Recordati Rare Diseases, the groups American subsidiary offers a portfolio of products for the treatment of a number of rare diseases as from 2013. Also in the U.S.A. the organization works closely with specialists, healthcare professionals, patients families and patient groups to meet the needs of people affected by these diseases and to spread the scarce knowledge available. Recordatis commitment to making its products available to patients suffering from rare diseases was recognized by the National Organization for Rare Disorders (NORD) in the U.S.A. with its 2011 Corporate Award. This important award was granted in recognition of the introduction into the United States of Carbaglu, the first specific treatment approved by the FDA (Food and Drug Administration) for NAGS deficiency, a very rare inherited metabolic disease.
RECORDATI RARE DISEASES ACADEMY - OUR COMMITMENT TO RARE DISEASES ( website)
The acquisition and diffusion of specific scientific knowledge is fundamental for the identification of a rare disease and is of great importance in the research for new therapies. Recordati is committed to support families suffering from the impact of a rare disease both through the research and development of new treatments as well as through the diffusion of knowledge within the scientific community.
Working in the field of rare diseases is an important responsibility to patients and healthcare professionals and we put this at the heart of our strategy. The Academy was launched to provide unconditional grants for training in rare disease. High-level courses are created under the authority of a scientific committee. The overall aim is to share experience in the management and outcome of rare disorders where individual experience is by its nature limited. The Academy offers specialists the opportunity to enrich their knowledge, develop new ideas and establish scientific relationships. Four live events are held each year bringing together clinicians and scientists from all over the world to discuss innovations and new diagnostic and management strategies. The Academy also provides online e-learning courses which aim to provide physicians, world-wide, with clinically useful and the most up-to-date information concerning current knowledge and recommendations for care.
"Remember.Research is the key to your cure!"
Healthwell Foundation Offers Financial Assistance To Acute Porphyria Patients
Sunday - December 27, 2015 @ 10:30:07
Healthwell Foundation Offers Financial Assistance To Acute Porphyria Patients
Krista Zodet, President HealthWell Foundation
We are pleased to join forces with the American Porphyria Foundation to increase porphyria awareness and spread the word about resources available through the HealthWell Foundation for people living with porphyria. Since 2006, the HealthWell Foundation has provided copayment and premium assistance to eligible acute porphyria patients. Through our fully-automated grants process, patients are able to determine eligibility and apply online. Patients also have the option to contact our hotline at 800-675-8416 to speak directly with a HealthWell representative. The HealthWell Foundation is an independent, 501(c)(3) charitable organization that provides financial assistance to insured individuals who struggle with high out-of-pocket medical expenses. You can learn more about the HealthWell Foundation by visiting us at www.HealthWellFoundation.org.
"Remember..Research is the key to your cure!"
Tracy Yelen ~ Research Experience with AIP
Thursday - December 24, 2015 @ 10:30:11
Tracy Yelen ~ Research Experience
Type of Porphyria:
Acute Intermittent Porphyria (AIP)
"If you're at all interested in what they are doing to me in this Panhematin trial, I am happy to share. During the entire stay, the medical team accessed my port. They drew all the blood they wanted without all the usual IV sticks, which is nice. Every morning after breakfast we did the infusions, which may or may not be a placebo. Neither the nurses nor I were allowed to see what was pumping into me. So I am blindfolded and there are sheets hung in the room to cover the medicine and tinfoil around the lines. It takes only a couple hours to complete. I snoozed and chatted with the sweet nurse. Outside of that, the dextrose fluids are flowing in through my port 24/7. Otherwise, it was pretty uneventful. Why do I tell you this? Basically, I want to remind you of how important it is to volunteer as a research patient if you ever get the opportunity. There are lots of trials that even perfectly well people can do for various different studies and various different medical reasons."
~Tracy Yelen, AIP
We need Acute Porphyria Research Volunteers for the Panhematin study. Please call the APF to learn more 1-866-APF-3635
"Remember.Research is the key to your cure!"
We wish you a Merry Christmas, Happy Holidays and a Happy, Healthy New Year!
Friday - December 18, 2015 @ 10:30:28
We wish you a Merry Christmas, Happy Holidays and a Happy, Healthy New Year!
It has been our pleasure to provide you and your families with the most up to date porphyria information available and to offer support for your needs. We also have enjoyed meeting so many of you over the past thirty years and have been blessed by the lasting friendships we have cultivated. We look forward to meeting many more of you and serving you in the future.
Please contact us if we can help in any way 713.266.9617!
Your friends at the American Porphyria Foundation.
"Remember.Research is the key to your cure!"
Who is the Scientific Advisory Board made up of?
Thursday - December 17, 2015 @ 22:50:26
Scientific Advisory Board
Who is the Scientific Advisory Board made up of? Please read the profiles of the Doctors. Please get involved in Research so you can meet An APF expert or a PTF DR.
The following doctors and scientists are participants in the APF Protect the Future program to develop the next generation of porphyria experts. They work directly with members of the APF Scientific Advisory Board as part of a rigorous program of study, clinical and laboratory work, research and publishing. Read more about this pioneering project.
Below is a list of some of the Porphyrias Research Consortium (PC) publications. The PC includes Drs. Karl Anderson, Montgomery Bissell, Joseph Bloomer, Herbert Bonkovsky, Robert Desnick, John Phillips. There are a number of other texts ready for publication. All PC members are also members of the APF Scientific Advisory Board. We hope as you read this list of publications, you will appreciate the depth of knowledge of our experts and their dedication to porphyria patients. At a recent meeting, the experts said, "Because our retirement is approaching, we must train as many future experts as possible lest our fifty years of expertise is lost."
RDCRN Porphyrias Consortium Publication List
Peer Reviewed
1. Gunn GB, Anderson KE, Patel AJ, Gallegos J, Hallberg C, Sood G, Hatch SS, Sanguineti, G: Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: case report and review of the literature. Head and Neck. 2010; 32:1112-7. PMID: 19536857; PMCID: PMC2891307
2. Hou W, Tian Q, Zheng J, Bonkovsky HL. Zinc mesoporphyrin induces rapid proteasome-mediated degradation of hepatitis C non-structural 5A protein in human hepatoma cells. Gastroent. 2010; 138:1909-19. PMID: 19909748; PMCID: PMC2860067
3. Jalil S; Grady JJ, Lee C, Anderson KE, Associations among behavior-related susceptibility factors in porphyria cutanea tarda. Clin Gastroenterol Hepatol. 2010; 8:297-302. PMID: 19948245; PMCID: PMC2834813
9. Hwang SI, Lee YY, Park JO, Norton HJ, Clemens E, Schrum LW, Bonkovsky HL. Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method. Clin Chim Acta. 2011; 412: 2241-2247. PMID: 21867695; PMCID: PMC3207492
10. Lakner, A, Bonkovsky HL, Schrum L. MiRNAs: fad or future of liver disease. World J Gastroent. 2011;17: 2536-42. PMID: 21633658; PMCID: PMC3103811
11. Li T, Bonkovsky HL, Guo J-T. Structural analysis of heme proteins: implications for design and prediction. BMC Struct Biol. 2011; 11:13. PMID: 21371326; PMCID: PMC3059290
12. Lorenzo FR, Phillips JD, Nussenzveig R, Lingam B, Koul PA, Schrier SL, Prchal JT. Molecular Basis of Two Novel Mutation Found in Type I Methemoglobinemia. Blood Cells Mol Dis. 2011; 46:277-81. PMID: 21349748; PMCID: PMC3075332
13. Phillips JD, Kushner JP, Bergonia HA, Franklin MR. Uroporphyria in the Cyp1a2-/- mouse.Blood Cells Mol Dis. 2011; 15:249-254. PMID: 21880518; PMCID: PMC3223295
14. Tian Q, Li T, Hou W, Zheng J, Schrum LW, Bonkovsky HL. Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells. J Biol Chem. 2011; 286:26424-30. PMID: 21659532; PMCID: PMC3143606
17. Wang Y, Langer NB, Shaw GC, Yang G, Li L, Kaplan J, Paw BH, and Bloomer JR: Abnormal Mitoferrin-1 expression in patients with erythropoietic protoporphyria. Exp Hematology. 2011; 39:784-794. PMID: 21627978; PMCID: PMC3143264
18. Wickliffe JK, Abdel-Rahman SZ, Lee C, Kormos-Hallberg C, Sood G, Grady JJ, Desnick RJ, Anderson KE, CYP1A2*1F and GSTM1 alleles are associated with susceptibility to porphyria cutanea tarda. Mol Med. 2011; 17:241-247. PMID: 20957336; PMCID: PMC3060985
22. Balwani M. Desnick R.J. The Porphyrias: Advances in Diagnosis and Treatment. Hematology Am Soc Hematol Educ Program. 2012; 2012:19-27. PMID: 23233556
23. Balwani M. Desnick R.J. The Porphyrias: Advances in Diagnosis and Treatment. Blood. 2012; 120:4496-504. PMID: 22791288; PMCID: PMC3512229
24. Singal AK, Kormos-Hallberg C, Lee C, Sadagoparamanujam VM, Grady JJ, Freeman DH, Anderson KE. Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol. 2012; 10:1402-9. PMID: 22985607; PMCID: PMC3501544
25. Singal AK, Gou E, Albuerne M, Hallberg CK, Anderson KE. Relapse of PCT after achieving remission with phlebotomy or low dose hydroxychloroquine. Hepatology 2013; 58:299A
26. Bonkovsky HL, Hou W, Steuerwald N, Tian Q, Parsons J, Hamilton A, Hwang S, Schrum L. Heme status affects human hepatic messenger RNA and microRNA expression. World J Gastroenterology 2013; 19: 1593-1601. PMID 23538684; PMCID: PMC3602476
34. Bissell DM, Lai JC, Meister RK, Blanc PD. Role of Delta-aminolevulinic Acid in the Symptoms of Acute Porphyria. Am J Med. 2014 Nov 8. Epub ahead of print PMID: 25446301
35. Besur S, Hou W, Schmeltzer P, Bonkovsky HL. Clinically important features of porphyrin and heme metabolism and the porphyrias. Metabolites, 2014; 4:977-1006. PMID: 25372274
37. Phillips, J.D., Kushner, J.P. The porphyrias. In: Hematology of Infancy and Childhood, Saunders, 2008.
38. Sood G, Anderson KE: Porphyrias. in Crowther MA, Ginsberg J, Schunemann H, Meyer RM, Lottenberg R (eds): Evidence-Based Hematology, Hoboken, Wiley, 2008. pp 229-237.
39. Sood, G, Anderson KE: Porphyria Cutanea Tarda. In: Best Practice, BMJ Publishing Group, 2008.
40. Anderson KE, Sood, G: Acute intermittent porphyria. In: Best Practice, BMJ Publishing Group, 2008.
41. Phillips, J.D., Anderson, K. Porphyria. In: A practical handbook to Williams Hematology, McGraw-Hill 2010, Chapter 57, pp 839-863.
42. Phillips JD, Anderson KE. The porphyrias (Chapter 57). In: Kaushansky K, Lichtman MA, Beutler E, Kipps TJ, Seligson U, Prchal JT, eds. Williams Hematology, 8th edition. New York: McGraw-Hill 2010: 839-863.
43. Anderson KE, Lee C, Balwani M, Desnick RJ. The porphyrias (Chapter 85). In: Kliegman RM, Stanton BMD, St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics, 19th edition. Philadelphia: Elsevier, 2011, pp 517e1-e17.
44. Anderson KE. The porphyrias (Chapter 217). In: L. Goldman and A.I. Schafer, eds. Goldmans Cecil Medicine, 24th edition, Philadelphia, Elsevier Saunders 2012:1363-71.
45. Lourenco, CM, Lee, C, Anderson KE. Disorders of heme biosynthesis (Chapter 37). In: Saudubray J-M, Van den Berghe G, Walter, JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 5th edition. Berlin:Springer-Verlag; 2012: 519-532.
46. Phillips, J.D. Side chain modification during heme biosynthesis. In: Handbook of Porphyrin Sciences, Academic Press 2012, Vol. 19, Chapter 91, pp 283-337.
47. Bonkovsky HL, Hou W, Guo J-T, Narang T, Thapar M. Porphyrin and heme metabolism and the porphyrias. In Wolkoff A, Lu S, and Omary B (Eds). Comprehensive Physiology, 3:1-37, 2013. PMID: 23720291
48. Gou E, Anderson KE. The Porphyrias. In: Hamblin MR, Huang YY, eds. Handbook of Photomedicine. Philadelphia, CRC Press, Taylor and Francis, 2014: 123-132.
49. Besur S, Bonkovsky HL. The porphyrias. Encyclopedia of Life Sciences, John Wiley and Co, London, UK, 2014.
50. Bissell DM. The porphyrias. In Rosenberg RN, Pascual JM, eds. Rosenbergs Molecular and Genetic Basis of Neurological and Psychiatric Disease, 5th Edition. Academic Press, Chapter 66, pp 725-43. 2014.
51. Desnick RJ, Balwani MB, Anderson KE. Heme Biosynthesis and the Porphyrias. In: Liver Diseases in Children, Fourth Ed., Suchy FJ, Sokol RJ, Balistreri WF, eds., Cambridge University Press, 2014:509-525
52. Anderson KE. Clinical and Laboratory Diagnosis of the Porphyrias, In: Ferreira GC, Kadish KM, Smith K, Guilard R eds. Handbook of Porphyrin Science. Hackensack, World Scientific Publishing Co., 2013: 370-415
53. Anderson KE. Porphyrias acute manifestations, In: Loriaux L, ed. Endocrine Emergencies. New York, Springer/Humana Press, Contemporary Endocrinology Vol. 74, 2014: 241-261.
54. Singal AK, Phillips J. Porphyria cutanea tarda and related disorders. In: The Porphyrins Handbook. Eds. Kadish K, Smith K, Guilard R, Ferrira G, Elsevier Science, 2014; 29: 219-262
Online resources
55. Anderson KE: Porphyria an Overview. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2010
56. Bloomer JR. ALAD Porphyria. National Organization for Rare Disorders (NORD) Database, Danbury, CT, 2010.
57. Singal, AK, Anderson KE: Porphyria cutanea tarda and hepatoerythropoietic porphyria. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2010
67. Anderson KE: ALA dehydratase porphyria. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2013.
68. Anderson KE: Porphyria, variegate. National Organization for Rare Disorders (NORD) Rare Disease Database, Danbury, CT, 2010, updated 2013.
69. Balwani M, Bloomer J, Desnick RJ. Porphyrias Consortium of the RDCRN. X-Linked Protoporphyria. Gene Reviews, 2013. PMID 23409301
70. Liu L, Phillips J, Bonkovsky HL. Porphyrias Consortium of the RDCRN. Porphyria Cutanea Tarda, Type II. Gene Reviews, 2013. PMID 23741761
71. Liu L, Phillips J, Bonkovsky HL. Porphyrias Consortium of the RDCRN. Hepatoerythropoietic Porphyria. Gene Reviews, 2013. PMID 24175354
72. Singal AK, Anderson KE: Porphyrias Consortium of the RDCRN. Variegate Porphyria. Gene Reviews, 2013. PMID 23409300
73. Erwin A, Balwani M, Desnick RJ: Porphyrias Consortium of the RDCRN. Congenital Erythropoietic Porphyria. Gene Reviews, 2013. PMID 24027798
Presented Abstracts
74. Bishop DF, Tchaikovskii V, Nazarenko I, Balwani M, Doheny D, Desnick RJ. Expression and characterization of the ALAS2 carboxy-terminal gain-of-function mutations causing X-linked Protoporphyria. Presented at the 12th International Congress of Human Genetics/The American Society of Human Genetics 61st Annual Meeting, Montreal, Canada, October 14, 2011.
75. Doheny D., Nazarenko I., Balwani M., Liu L., Naik H., Anderson K., Bissell D.M., Bloomer J., Bonkovsky H., Kushner J., Phillips J., Bishop D., Desnick R.J. Erythropoietic Protoporphyrias: Frequency of Mutations in the Ferrochelatase Gene Causing Autosomal Recessive Erythropoietic Protoporphyria and Mutations in the 5-Aminolevulinate Synthase 2 Gene Causing X-Linked Protoporphyria. Presented at the 12th International Congress of Human Genetics/The American Society of Human Genetics 61st Annual Meeting, Montreal, Canada, October 13, 2011.
76. Hou W, Tian Q, Lu QL, Schrum WL, Bonkovsky HL. Zinc protoporphyrin, a novel endogenous HCV NS3-4A protease inhibitor, displays anti-viral activity. Presented at the 62ndAnnual Meeting of AASLD, San Francisco, CA, November 4-8, 2011.
77. Tian Q, Hou W, Steuerwald NM, Schrum WL, Bonkovsky HL. Heme markedly up-regulates RNA-binding motif protein 24 gene expression in human hepatocytes. Presented at the 62ndAnnual Meeting of AASLD, San Francisco, CA, November 4-8, 2011.
78. Tian Q, Hou W, Zheng J, Schrum WL, Bonkovsky HL. LONP1-dependent breakdown of mitochondrial 5-aminolevulinicacid synthase protein by heme in human liver cells. Presented at the 62nd Annual Meeting of AASLD, San Francisco, CA, November 4-8, 2011.
79. Hwang S-I, Lee Y-Y, Park J-O, Norton HJ, Clemens E, Schrum LW, Bonkovsky HL. The measurement of hepcidin from human urine and serum to study effects of a single dose of oral iron by an optimized LC-MS/MS method. Presented at the 62nd Annual Meeting of AASLD, San Francisco, CA, November 4-8, 2011.
80. Singh, A, Pierson, K, Wilkinson, G, Anderson, K. Porphyrias: Prevalence and Frequency of Testing in a National Health Care Database. Presented at the 63rd Annual Meeting of AASLD, Boston, MA, November 9-13, 2012.
81. Ludtke A, Yasuda M, Lin G, Clavero S, Nazarenko I, Jungmin K, Doheny D, Balwani M, Desnick RJ. Acute Intermittent Porphyria: Identification of 23 Novel Hydroxymethylbilane Synthase Mutations and Functional Characterization of Six Novel Missense Mutations. Presented at the ACMG Annual Clinical Genetics Meeting, Phoenix, AZ, March 19-23, 2013.
82. Balwani M, Bishop DF, Nazarenko I, Yasuda M, Doheny D, Dailey HA, Liu L, Anderson KE, Bissell DM, Bloomer JR, Bonkovsky HL, Phillips JD, Desnick RJ. Mutation analysis of 155 North American Patients with Erythropoietic Protoporphyria reveals novel Ferrochelatase Mutations and a high prevalence of X-Linked Protoporphyria due to previous and novel 5-Aminolevulinate Synthase 2 mutations. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
83. Balwani M, Naik H, Peter I, Anderson KE, Bissell DM, Bloomer JR, Bonkovsky HL, Phillips JD, Desnick RJ. Erythropoietic Protoporphyria and X-Linked Protoporphyria in the United States: Results from the Longitudinal Study of the NIH/RDCRN Porphyrias Consortium. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
84. Bishop DF, Tchaikovskii V, Nazarenko I, Desnick RJ. Molecular Expression and Characterization of Erythroid-Specific 5-Aminolevulinate Synthase Gain-of-Function Mutations Causing X-Linked Protoporphyria. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
85. Gou EW, Singh A, Pierson KS, Wilkinson GS, Anderson KE. Frequency of Porphyria Testing in a National Health Care Database. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
86. Larion S, Caballes FR, Hwang S-I, Lee J-G, Rossman WE, Parsons J, Steuerwald N, Li T, Maddukuri V, Yazici C, Groseclose G, Finkielstein CV, Bonkovsky HL. Circadian rhythms in acute intermittent porphyriaa pilot study. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
87. Mittal S, Yasuda M, Desnick RJ, Anderson KE. Metabolic Analysis in Transgenic Mouse Models of Acute Intermittent Porphyria (AIP). Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
88. Naik H, Balwani M, Doheny D, Liu L, Desnick RJ. Experience with a Pilot Skype Internet Support Group for Symptomatic Patients with Acute Intermittent Porphyria. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
89. Ludtke A, Yasuda M, Gan L, Clavero-Villarrub S, Nazarenko I, Kim J, Doheny D, Balwani M, Desnick RJ. Acute Intermittent Porphyria: Identification of 19 Novel Hydroxymethylbilane Synthase Mutations and Functional Characterization of Four Novel Missense Mutations. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
90. Maddukuri VC, Yazici C, Anderson KE, Bissell DM, Bloomer JR, Desnick RJ, Phillips JD, Naik H, Gandolfo L, Light C, Bonkovsky HL. Acute intermittent porphyria [AIP] in the United States: features of the first 82 cases enrolled in the longitudinal study of the porphyria consortium [PC]. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
91. Phillips JD, Warby C, Bergonia H, Marcero J, Parker C, Franklin M. Porphyria studies in Cyp1A2-/- and wild type mice suggest that heme regulation of ALA-synthase transcription and mitochondrial membrane translocation can be separated based on heme supply-and-demand. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
92. Singal AK, Jampana SC, Kormos-Hallberg C, Anderson KE. Low-dose hydroxychloroquine to treat or prevent relapse of porphyria cutanea tarda during hepatitis C treatment. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
93. Singal AK, Gou EW, Albuerne M, Kormos-Hallberg C, Anderson KE. Relapse of porphyria cutanea tarda after achieving remission with phlebotomy or low dose hydroxychloroquine. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
94. Yazici C, Maddukuri VC, Anderson KE, Bissell DM, Bloomer JR, Desnick RJ, Phillips JD, Naik H, Gandolfo L, Light C, Bonkovsky HL. Hereditary coproporphyria [HCP] and variegate porphyria [VP] in the United States: Initial results from the longitudinal study of the porphyria consortium [PC]. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
95. Wang B, Bissell DM, Lai J, Cimino T, Porphyrias Consortium. A Combined Clinical Index for the Diagnosis of Acute Porphyria. Presented at the Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias, Lucerne, Switzerland, May 16-18, 2013.
96. Ludtke A, Yasuda M, Balwani M, Liu L, Arvelakis A, Naik H, Clavero S, Bishop D, Phillips J, Ramanujam S, Anderson K, Yu C, Florman SS, Desnick RJ. First US Orthotopic Liver Transplant for Intractable Acute Intermittent Porphyria. Presented at The American Society of Human Genetics 63rd Annual Meeting, Boston, MA, October 22-26, 2013.
97. Gou E , Weng C, Phillips JD, Balwani M, Bissell DM, Bloomer JR, Bonkovsky HL, Desnick RJ, Naik H, Anderson KE. Variability in erythrocyte and plasma porphyrin levels in erythropoietic protoporphyria and x-linked protoporphyria. Presented at the American College of Gastroenterology Annual Meeting, Philadelphia, PA, October 20-22, 2014.
As you all know, we are collecting EPP patient experiences in letter-form so that we can take them collectively to the FDA to ask them for the accelerated approval of the drug Afamelanotide. To date we have collected 214 patient letters with a few more on the way.
Please take a minute to write a letter today. You can scan or/and send it to us by replying to this email. You can also fax it to us at 713.840.9552. Today is the very last chance to make a difference!
Your contributions to previous letter campaigns worked. They convinced the FDA to approve Phase III of the drug trials in the USA, and our American letters helped convince the European Medicines Agency to grant approval of the drug in the European Union. Now it is our turn to seek approval for Afamelanotide by the FDA in the USA!
If you have any questions, please reach out to the APF 713.266.9617. Let's make this happen. Patient advocacy works. THANK YOU FOR PARTICIPATING!
"Remember.Research is the key to your cure!"
Patient Education Meeting in Orlando Florida a huge success
Monday - December 14, 2015 @ 10:30:00
Patient Education Meeting in Orlando Florida a huge success
The Patient Educational Meeting that we held last weekend in Orlando Florida in conjunction with the ASH convention, was a huge success. We had a great turn out there was standing room only! A special thank you to Drs Phillips, Parker and Silver, and the Recordati Company for coming to the meeting. The questions asked by the members were excellent, showing that the more you ask and the more you learn then the better equipped you are to care for yourself! We would like to thank the doctors who presented at the meeting as well as our long-term APF member Amy Chapman for helping us to organize it. Also, special thanks to everyone who attend with their families and friends.
Watch the APF E-news for the announcements about the upcoming meetings. Make sure your membership is up to date, so you receive all news.
Please get involved and take action now and sign up for research so that we can learn more and ultimately find a cure!
Researchâ?¦.is the key to your cure!
An update of clinical management of acute intermittent porphyria
Friday - December 11, 2015 @ 10:30:01
An update of clinical management of acute intermittent porphyria
Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma.
Acute intermittent porphyria (AIP) is a rare inherited metabolic disease due to a deficiency of the hydroxymethylbilane synthase (HMBS) in heme biosynthesis.1 AIP manifests after the puberty with occasional neuropsychiatric crises associated with accumulation of porphyrin precursors such as δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) which are released from the liver into the circulation1,2 (Figure 1). The diagnosis is often delayed, because clinical manifestations are unspecific2 and commonly mimic acute encephalopathy or abdominal crisis of other origin.3
Precipitating factors and pathogenesis of an acute attack in AIP.
AIP is the most common type of acute porphyrias in most of the countries worldwide.1 The major clinical manifestation of AIP is an acute attack, which is clinically indistinguishable from those caused by other acute porphyrias: variegate porphyria (VP) and hereditary coproporphyria (HCP).2 The management of an acute attack in each disease is similar,2 and thus, more specific classification of an acute porphyria can be done in remission. Photosensitivity and skin fragility found in patients with cutaneous porphyrias, VP and HCP, occur independently of acute attacks and do not occur in AIP.4,5
When acute porphyria is suspected, biochemical plasma or urinalyses of porphyrin precursors are mandatory to confirm the diagnosis of an acute porphyric attack.2 More than five-fold elevation of urinary PBG excretion together with typical symptoms of an acute attack is sufficient to start a treatment,6 but in each case other causes of abdominal crisis must be excluded before a specific treatment of an acute attack is administered. Plasma porphyrin spectrum is a valuable tool to confirm the diagnosis in the early phase and helps to identify different subtypes of acute porphyrias during an acute attack.7 In AIP emission peak is only transient, and if taken late, may be negative leading to misdiagnosis. AIP and HCP cannot be distinguished by plasma analysis. Mutation screening can be done at the quiescent phase of the disease (Table 1).
The laboratory investigations to confirm AIP and other acute porphyrias
Currently, the prognosis of patients with AIP is good even in severe attacks,3,812 but physicians should be aware of a potentially fatal outcome of the disease.10 During remission the majority of the patients experience no clinical symptoms. Hypertension, chronic kidney insufficiency, chronic pain syndromes, and hepatocellular carcinoma (HCC) may be long-term complications of AIP.3,8,1315
The management of patients with AIP include following strategies:
During an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, sensorimotor neuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy.
During remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members which can diminish mortality and prevent subsequent attacks among them.
Management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in AIP patients with severe recurrent attacks.
Follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and HCC.
Clinical manifestations and pathogenesis of an acute attack
The majority of acute attacks manifest as a combination of abdominal pain, mild mental symptoms, and autonomic dysfunction.2,6 Both acute peripheral neuropathy and severe encephalopathy may develop, if an acute attack proceeds10,11,16 (Figure 2). It is usually iatrogenic, mainly due to administration of porphyrinogenic drugs when the diagnosis of acute porphyria is delayed.10,11,16 Both endogenous and exogenous factors, such as certain medications, alcohol, infections, low caloric intake, or changes in sex hormone balance during the menstrual cycle or pregnancy, can provoke clinical manifestations in AIP8,17 (Figures 1 and and2).2). All these factors induce heme synthesis either directly or indirectly via activation of ALA synthase in the liver18 resulting in accumulation of porphyrins and their precursors in the tissues and circulation.
Staging of an acute attack in connection with precipitating factors and recommendations of heme therapy.
Excess of ALA is the most potential candidate to cause neuronal damage and could be responsible for autonomic and peripheral neuropathy and encephalopathy via multiple mechanisms.19 Results from both the experimental and clinical data support the direct neurotoxicity of ALA, but also modification of γ-aminobutyric acid (GABA)-ergic system due to the structural similarity of ALA and GABA/glutamate,20 as well as formation of free radicals and reactive oxygen species from ALA21 may play a role in the pathogenesis of an acute attack.
Heme preparations, in the current treatment, lead to a rapid decrease of synthesis of porphyrin precursors via negative feedback (Figure 1).6 Reduced transcription of ALA synthase in the liver achieved by heme results in cessation of an acute attack within few days.6 Dose-dependent administration of glucose has also been shown to downregulate ALA synthase in experimental conditions via peroxisome-proliferator-activated receptor γ coactivator 1α (PGC-1α), a protein which directly induces transcription of ALA synthase 1.22Subsequently, glucose infusions have been used to prevent fasting and may be sufficient in mild attacks. Despite the fact that recombinant human-HMBS-enzyme (rh-HMBS) therapy decreased the plasma level of PBG rapidly, it had no effect on the ALA level23 or the patients acute symptoms. In contrast, liver transplantation immediately corrects porphyrin metabolism to normal demonstrating the dominant role of liver as a source of ALA.24
The exact mechanism of cyclic attacks in women is unknown. Despite the level of sex hormones is at the highest during the second and third trimester, acute attacks are rare during pregnancy.3,8,17,25 Although, especially, progesterone is known to be a potent inducer of ALA synthase,26 the direct role of sex hormones as sole precipitating factors is unlikely.27 Moreover, cyclical attacks occur mainly in premenstruum when the levels of estrogen and progesterone fluctuate the most, and usually are resolved during early menstruation.8,17 Individual variation in the progesterone metabolism may play a role in clinical manifestations of AIP.28 Cytochrome-P450 activities in the liver also vary individually and can result in an abnormal level or ratio of sex hormones affecting the feedback mechanism to hypothalamus. Several neurotransmitters control the menstrual cycle through the regulation of pulsatile release of gonadotropin-releasing hormone (GnRH) and other clock mechanisms in the hypothalamus.29 This interaction may activate abnormal liver metabolism,30 and consequently precipitate acute attacks by the central mechanism making AIP a central nervous system disorder in addition to a liver disease.27
The clinical criteria of an acute attack include the paroxysmal nature of the symptoms with abdominal or back pain associated with one or more signs of autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms6 (Table 2).
The biochemical criteria of an acute attack include more than a fivefold increase of urinary PBG excretion (Table 1), which can be detected by a simple Watson-Schwartz or Hoesch qualitative test.31 The results should be confirmed by a quantitative measurement of urinary PBG, since false positive results in these screening tests are possible, especially, if perchloric acid instead of amyl alcohol is used as an extract.3133If the urine samples are not sheltered from the light, urinalysis may become false negative.3133
Urinary excretion of PBG is elevated in 88% of the patients with AIP in remission.34 During an acute attack PBG excretion increases commonly at least two- to fourfold from the values found in remission.34 Urinary ALA is always increased during an acute attack but remains elevated only in 61% of AIP cases in remission.34 In AIP, urinary excretion of uroporphyrins is increased, including both I and III isomers, and exceeds that of coproporphyrins I and III.34
Of note, abnormal metabolism of porphyrin and their precursors may also be detected in patients with hepatopathy or heavy metal intoxications.31,35 The clinical manifestations may even resemble AIP,36 but biochemically only a mild to moderate coproporphyrinuria is present, and porphyrin precursors are commonly only transiently elevated.35,36 If urinary ALA level exceeds that of PBG significantly, lead intoxication should be excluded.31
In AIP, plasma porphyrin emission spectrum test with excitation wave length of 405 nm shows a peak at 615620 nm during an acute attack similar to HCP but it can be less frequently found in remission.32,34Emission peak is due to porphyrins ability to absorb light at wave length around 400 nm and their emission as red fluorescence, at around 600 nm.37 Plasma emission spectrum test is used mainly to exclude symptomatic V P, since it has a unique 624627 nm spectrum due to protein-associated plasma porphyrins.31,32,38 Of note, emission peak is commonly negative at the asymptomatic phase of VP.
Around 20% of the patients with AIP have moderately increased excretion of fecal protoporphyrin, which is less prominent than that of VP patients.5,34 Since fecal coproporphyrin level is usually normal in AIP,34more than tenfold excretion of coproporphyrin (isoform III:I >2) in feces together with protoporphyrin suggests HCP.4
In 84%95% of patients with AIP,34,39 erythrocyte HMBS (Erc-HMBS) activity has been lower than normal. In the variant form of AIP (5%16% of all patients),34,39 Erc-HMBS activity was normal due to an alternative splicing of the HMBS gene in erythroid cells.40 HMBS activity should be assayed in remission, since erythropoiesis may be enhanced during an attack as well as in hypochromic or hemolytic anemias and hepatopathy.33,41 In contrast, it can be decreased in non-porphyric individuals with sideropenia.33
DNA analysis is the most reliable method to confirm AIP in the patients and their symptom-free relatives.34,42 The direct sequencing of the HMBS gene is used to identify a mutation in the proband and the asymptomatic gene carriers among the family members.42 The sensitivity of the mutation analysis is 90%100%.34,43,44 To date, 391 mutations have been reported in the HMBS gene,45 and therefore DNA testing in an index case of a family is perhaps more laborious and time consuming, but afterward mutation analysis may easily reveal several family members at risk.
Current treatment options include heme preparations during an acute attack, which may be life-saving, especially if encephalopathy or polyneuropathy develop.2 The treatment should be started immediately during a severe or moderate acute attack after the demonstration of typical symptoms of acute porphyria and more than fivefold elevation of urine PBG shown by qualitative tests.6 Other causes of abdominal crises and neuropsychiatric symptoms often demanding other specific and rapid interventions should always be excluded.
Only around 30%50% of the patients with a mutation in the HMBS gene have mild or moderate clinical symptoms of AIP during their life span.8,17,46 Less commonly, around 3%5% of the patients with AIP17,47 have recurrent severe attacks, and no time for neuronal recovery. These patients are at a high risk for chronic pain syndrome. The onset and clinical outcome of an attack is commonly influenced by several exogenous factors simultaneously, and endogenous factors, such as the residual activity of a mutated protein, individual differences in other metabolic pathways in the liver and in neuronal protection capacity, may modify the clinical outcome.12,34
Heme preparations have been used for acute attacks for more than three decades without tolerance.3,6,48,49Hemin is isolated and purified from human red cell concentrates. In Europe, Asia, and South Africa, hemin is commercially available as heme arginate (Normosang, Orphan Europe SARL, Puteaux, France) and in Northern America as lyophilized hematin (Panhematin, Ovation Pharmaceuticals Inc., Deerfield, IL, USA).
In an open series of 22 patients, the patients treated with heme arginate6 recovered more rapidly in comparison with those treated with glucose infusions in the earlier series.5053 Safety and efficiency of lyophilized hematin has also been demonstrated in six open-labeled studies involving over 200 AIP patients.48 The only study using a placebo-controlled series found insignificant benefit of heme arginate for the analgesic requirement, pain score, and duration of the hospital stay.54 The validity of the trial has been questioned6 due to small number of patients (eleven patients treated with heme and ten with a placebo), a high proportion of the patients with peripheral neuropathy in this series (43%), delayed administration of preparation (>2 days after admission), and difficulties in arranging a placebo, which resembles heme arginate.
Heme arginate and lyophilized hematin are usually infused daily (34 mg/kg) into a large peripheral vein or venous access port for 34 consequent days, but a repetitive course may be required if porphyric symptoms are still progressing6,48 (Table 3). Concentrated solution of heme arginate is mixed with 100 mL physiological saline, and lyophilized hematin is reconstituted with sterile water before infusion.6,48,55Lyophilized hematin should be used immediately after reconstitution. Heme arginate should also be used soon after dilution, since it becomes unstable and may aggregate. In both cases, addition of human serum albumin may be beneficial in order to diminish the risk of phlebitis at the site of infusion. After infusion, the vein should be washed with saline for 1015 minutes. For the long-term use of heme, a central access catheter (tunneled catheter or portacat) may be useful. Low molecular weight heparin can be used subcutaneously to prevent or treat thrombophlebitis.
Clinical manifestations and treatment of an acute attack
The treatment with heme preparations should be started without delay, but even in the late stage of progressing motor neuropathy, it is efficient.10 If a patients neurological condition has stabilized (plateau phase, Figure 2), an additional treatment with heme is rarely necessary but other causes such as infections may deteriorate the patients clinical condition and should be treated properly.
The reported side effects include mild coagulopathy,56 thrombophlebitis,6 and anaphylactic shock in one case.57
High carbohydrate loading and supportive treatment
The treatment of acute attacks with high carbohydrate diet or infusions (300500 g/day) has been in use in order to downregulate the activity of ALA synthase and prevent fasting.58 High dose of glucose should be infused continuously 24 hours per day with an automatic syringe, and blood sugar level should be monitored regularly to avoid hyper- or hypoglycemia causing additional neurological complications. If a patient is able to eat, carbohydrate rich meals may similarly have a beneficial effect.
Currently, the use of glucose is limited only to mild attacks (ie, mild pain, no paresis, seizures, or hyponatremia) according to the guidelines for the treatment of an acute attack in the USA and South Africa, or if heme arginate or hematin are not available locally11,59 (Table 3). In mild cases, the dose of glucose can be lower than discussed earlier. If glucose infusions do not result in clinical remission within a day or two, or if an acute attack is severe at the onset, heme preparations should be used. Mild or clearly resolving attacks with minor pain or anxiety may be treated symptomatically.60
Low to moderate dose of glucose and saline infusions should be used as supportive treatment to prevent dehydration and during fasting if the patient is unable to drink.49 The amount of daily fluids may vary from restricted fluid intake in a case of inappropriate antidiuretic hormone secretion to rapid restoration of intravascular volume and correction of electrolyte disturbances in rhabdomyolysis-induced renal failure.61Thus, fluid restoration must be tailored individually and careful monitoring of water and electrolyte balance, including sodium, potassium, and magnesium, and renal function should be done (Table 4). Mild to severe hyponatremia is a rather common phenomenon (25%60%) during an acute attack,10,11,5053 and should be corrected slowly (<12 mmol/L/24 h)61,62 because of potential pontine myelinolysis, a condition also described in a patient with AIP.62
Signs, symptoms, and metabolites followed during an acute attack
Rhabdomyolysis during an acute attack is often neglected,61 but can be easily diagnosed by measurement of plasma myoglobin or creatinine kinase level and should be treated according to the guidelines. Acute kidney insufficiency is a rare but a severe complication of an acute attack, and may proceed to hemodialysis.11,15,63
All potentially precipitating factors such as drugs, smoking, and alcohol should be eliminated during an acute attack. Infections should be treated promptly and caloric intake of a patient should be sufficient to avoid fasting.2,49,59 Administration of porphyrinogenic drugs commonly results in proceeding of an acute attack to neuropathy or encephalopathy (Figure 2). Several lists of potentially safe and unsafe drugs are available on the Internet.6467
Some drugs, such as barbiturates and sulfonamides, are strictly forbidden since their use has been associated with several severe attacks. Most of the drugs, however, are classified as potentially porphyrinogenic, since clinical data about their safety in acute porphyria is lacking. The majority of the patients, especially asymptomatic, tolerate many drugs well; thus, total avoidance of drugs for the safety reasons leads to inappropriate treatment of patients other diseases. Antibiotics excluding sulfonamides, drugs for cardiovascular diseases, and pain killers are usually well tolerated in addition to preparations used in oncology. The follow-up of urinary excretion of porphyrin precursors may elucidate the effect of a drug on the heme biosynthesis but increased excretion of porphyrin metabolites without clinical symptoms should not solely determine its use. In each case the potential risk and advantage of a drug should be evaluated by a clinician.
Symptomatic therapy for pain, hypertension, tachycardia, nausea, and vomiting is commonly required (Table 3).2,49 Abdominal pain is usually intensive (visual analog scale, VAS >7 cm, scale from 0 to 10 cm)68 and opiates are needed. Morphine, pethidine, oxycodone, tramadol, and fentanyl have been used without complication. Paracetamol and anti-inflammatory drugs can be used in mild cases.
Beta blockers are commonly used for tachycardia and to prevent arrhythmia. If a hypertensive crisis develops, it can be treated with beta blockers or clonidine or other drugs recommended by the current guidelines.69 Nausea and vomiting can be controlled by olanzapine, lorazepam, or prochlorperazine.2,49Domperidone has been used during an acute attack, but interactions with opiates and other drugs increasing the risk for arrhythmias may prevent its use. Metoclopramide has been associated with neuropathy and encephalopathy during a few acute attacks,70 but some patients have used it without complications.66Urinary retention is quite common and can be treated with catheterization. Blood pressure, heart rate, pain score by visual analog scale,68 and severity of the muscle weakness should be evaluated daily at the bed side. Bulbar paresis, proceeding muscle weakness, and arrhythmia are signs of progression of an acute attack and the patient should be transferred to the intensive care unit.10 Respiratory insufficiency as a sign of motor neuropathy increases risk of pneumonia and may require early mechanical ventilation. Patients with paresis due to neuropathy or encephalopathy require rehabilitation therapy even in the early phase.
Epileptic seizures, which are usually generalized, can be treated with intravenous diazepam, gabapentin, levetiracetam, or propofol if status epilepticus develops.2,49,59 Usually there is a single or few transient seizures, which associate with acute encephalopathy visualized as posterior reversible syndrome in brain magnetic resonance imaging (MRI) and does not require anticonvulsive treatment in the follow-up.16Correction of hyponatremia may be beneficial in patients with seizures (Tables 3 and and4).4). Insomnia and anxiety are usually mild and do not require additional medications but can be treated with benzodiazepines, such as lorazepam.49 Hallucinations are also signs of acute encephalopathy and should be treated with phenothiazine or olanzapine.
Duration of the diagnostic delay of an acute attack correlates with a fatal outcome10 mainly due to the administration of drugs known to precipitate AIP for a misdiagnosed attack. The causes of death are related to complications of prolonged ventilation and cardiac arrest.10,11,50,51,53 The majority of patients display full functional recovery even after a severe attack.10
The mortality has decreased dramatically during the last decades among diagnosed AIP patients by 5%20% during an acute attack,3,811 but it is still a potentially fatal disease.
In remission, patients may tolerate medications classified as potentially unsafe and alcohol, but if porphyric symptoms appear their use should be restricted.8,17,49 The education of patients and their family doctors about precipitating factors, including the information of safe and unsafe drugs, necessity of prompt treatment of infections, healthy lifestyle with regular normocaloric diet, avoidance of alcohol, if porphyric symptoms occur, and smoking, reduction of excessive stress are essential for patients prognosis.8,17,49 In the treatment of obesity, the patients with AIP should include carbohydrates into their diet, and the weight reduction should be done slowly.
DNA diagnostics among family members is recommended before the adulthood, since it decreases the likelihood of an acute attack to 5% in patients diagnosed at the presymptomatic phase.12 The prenatal screening in families with AIP is not recommended because of a low risk of severe attacks among mutation carriers12 and good therapy options even if acute attacks would develop.49
In women with AIP, the menstrual cycle is the most common precipitating factor (10%39%) manifesting usually with 13 months interval in premenstruum.8,17 In the majority cases, these attacks are mild and do not require hospitalization. Irregular cycles due to hormonal imbalance may predispose to cyclical attacks. However, in 3%5% of the women cyclical attacks are severe and frequent (up to 24 weeks interval),17,47which disable their lives. If the patient has recurrent attacks preventive therapy is needed.
Evaluation of the lifestyle
Usually these women have several precipitating factors simultaneously. It is important to first correct lifestyle, indicating cessation of smoking and use of alcohol or any medication or homeopathic drug which may be porphyrinogenic. Since body mass index (BMI) is commonly at the low or low normal level among women with recurrent attacks, gaining weight, at least a few kilos, may be beneficial to balance energy metabolism. Patients should avoid fasting and potential hypoglycemia by regular eating habits.
Evaluation of hormonal therapy in women
The exogenous hormonal therapy can be used, if lifestyle changes are insufficient to prevent attacks. Contraceptive pills have been used for prophylaxis of recurrent acute attacks for many years,8,71 but not all women respond to this therapy even after 3 months of use. We have used ethinyl estradiol-levonorgestrel preparation successfully, and the responders have tolerated them well, even for years. About 46%58% of the Finnish and Swedish women with AIP and VP have used hormonal pills for contraception,8,17 and the majority of them have had no complications in remission despite use of various progesterone compounds in combination with estrogen preparations. Intrauterine devices including levonorgestrel have not been reported to cause porphyric symptoms.17 Based on our results, we have let our patients use hormonal contraception under supervision.
Of note, contraceptive pills can also provoke acute attacks in 5%14% of the women with both latent and manifest AIP (24% of selected women with previously manifest AIP),8,17 and as such many guidelines recommend not to use them.49,66,67 Tolerance to progesterone preparations may vary individually but estrogen preparations, especially used for menopausal symptoms, do not usually precipitate porphyric symptoms.17,71 Thus, it is important that the risk for potential complications and benefits of hormonal therapy are evaluated individually by a clinician. Excretion of porphyrin precursors should be controlled and hormonal preparations should be stopped, if symptoms suggestive for acute porphyria occur during their use.
In contrast, GnRH analogs inducing ovarian suppression are not porphyrinogenic and have been reported to diminish the severity and frequency of attacks in 60%80% of the women.7275 The responders have more frequently had regular menstrual cycles and pronounce decrease in the estradiol level after the treatment with GnRH analogs when compared to the women who have been nonresponders or have responded only to a high dose of the preparation.72,73 Drug-induced menopause decreased the excretion of porphyrin precursors to 60% of the previous values in both groups.
The treatment should first be continued up to a few months, and thereafter its efficiency should be evaluated. If a longer period for treatment is needed, GnRH agonist can be combined with estrogen preparations to avoid osteopenia and other menopausal symptoms. Estrogen patches are preferred to avoid the first passage metabolism in the liver. Progesterone should be administered regularly to avoid increased risk of endometrial cancer during the postmenopausal estrogen therapy, but they may also induce acute attacks during the combination treatment.74 Intrauterine device with levonorgestrel has been used without complications in this compound hormonal therapy,74 and another option is to lower the dose of GnRH analogs to sustain natural sex-hormone level, which could prevent the long-term side effects of the GnRH agonist.17,74 The patients should be followed carefully and efficiently, and side effects and need for the combination therapy should be evaluated at regular intervals. Women with cyclical attacks may also become asymptomatic after their natural menopause.17 Screening of urinary excretions of PBG and ALA may elucidate the biochemical activity of the disease, and maybe useful to follow.
Prophylactic heme therapy
Regular heme infusions commonly alleviate the severity and frequency of recurrent attacks.2,3,49 The aim of this treatment is to decrease substantially the level of porphyrin precursors in plasma. The majority of patients respond well but the long-term treatment may induce dependence on the exogenic heme. As a result, a patient may have increased need for heme from monthly to twice a week infusions and withdrawal of the treatment is difficult due to severe porphyric symptoms. Frequent administrations of heme preparations may lead to thrombotic complications of superficial veins, and assessment of a permanent central venous catheter may be necessary. Moreover, long-term treatment of heme may lead to iron overload and organ damage due to hemosiderosis. Progressing hepatopathy, heart failure, and endocrinopathies may develop. Follow-up of plasma ferritin and transferrin saturation levels is necessary, and computed tomography (CT) or MRI reveal iron load in organs. Venesections are usually poorly tolerated but iron chelates may be used.
Liver transplantation in AIP patients with severe recurrent attacks
If the standard treatment is unsuccessful or quality of life is unbearable, liver transplantation is an option for severely affected patients.24,49 Currently, more than ten AIP patients have undergone liver (or liver-kidney) transplantation since 2004.24,49,76 It has been successful in the majority of cases resulting in immediate correction of abnormal porphyrin metabolism and cessation of attacks and chronic pain syndrome.24Immunosuppressive drugs have been tolerated well by the patients, and their quality of life has improved dramatically. A few patients have died soon after liver transplantation mainly due to infections. Timing is also important in the liver transplantation. Patients should not wait too long in a too poor condition since the recovery from the operation and immunosuppression may associate with early complications such as infections or thromboembolic complications.76 If chronic motor neuropathy and encephalopathy have been present for years, the full recovery of neuronal damage may not be reached even after total normalization of porphyrin metabolism. Of note, partial liver transplantation has not corrected biochemical abnormalities or clinical manifestations permanently and should not be done.77 Moreover, transplantation of the HMBS deficient liver induced an abnormal porphyrin metabolism in a recipient.77
Previously, pregnancies were commonly complicated by acute attacks mainly during the first trimester and postpartum, and women with AIP were advised to avoid pregnancy. Currently, overall prognosis for pregnancy in AIP is good, especially if the diagnosis is known in advance and no porphyrinogenic drugs are used.8,17,25
Cyclical attacks do not predict attacks during pregnancy, and pregnancy nowadays seldom precipitates acute attacks.8,17,25 Heme preparations have been used during pregnancy without fetal or maternal complications.11,27,49,78 In some women, who have experienced cyclical attacks for many years, recurrent attacks have stopped after the first trimester of pregnancy, and these women have been asymptomatic thereafter.17,27 Thus, pregnancy may act as a hormonal therapy and could be even considered as an option for the women with cyclical attacks.
The prevalence of hypertension is significantly higher in patients with manifest AIP than in general population.3,8,79,80 Thus, early monitoring of blood pressure and efficient treatment with antihypertensive drugs is mandatory to avoid organ complications. This is especially crucial if renal failure is already present.
Monitoring of creatinine level in the follow-up of patients with manifested AIP shows mild to moderate elevation in 10%50% of the cases.8,79,80 This is significantly more common than in general population.3,8,9,15,63 Tubulointerstitial kidney disease has been the main presentation in a biopsy of the investigated cases.8,15,63 It has been commonly associated with recurrent acute attacks, hypertension, and use of anti-inflammatory drugs.8,15,63,80 The main recommendation for renal protection include adequate drinking regimen, blood pressure control, and avoidance of anti-inflammatory or other nephrotoxic drugs according to the general guidelines. Patients with AIP and nephropathy, even mild, have an increased risk of deterioration of renal functions during an attack, and should be treated carefully with fluid therapy and hemodialysis if necessary.
Chronic hemodialysis may induce cutaneous symptoms in patients with AIP mimicking porphyria cutanea tarda (PCT).81 Since mainly ALA and PBG but not porphyrins have been filtered during dialysis, recurrent attacks were transformed to cutaneous manifestations in one patient.81 Use of high-flux hemodialysis and erythropoietin substitution might be of help since they remove plasma porphyrins and have alleviated clinical manifestation in PCT patients with end-stage renal failure.82,83 Kidney transplantation84 or combined liver and kidney transplantation85 have been done successfully and should be done whenever needed. The patients who have undergone kidney or liver transplantation should be followed up regularly because of increased risks of renal failure, hypertension, and cardiovascular complications. Metabolic changes and osteoporosis may also develop. Skin cancers and lymphomas are more common than in the general population and thus, extensive exposure to the sunlight and smoking should be avoided. Long-term complications are often multifactorial but commonly related to immunosuppressive drugs in use.8688
Several population-based studies of AIP patients have shown an evidence of a significantly increased incidence of HCC in AIP compared to general population.14,15,8991 The highest incidence of HCC (23%27%, more than 60-fold increased risk compared to general population) was shown in the Finnish and Swedish patients with AIP.13,89,91 In contrast to renal insufficiency, HCC has developed in patients with both symptomatic and asymptomatic AIP, although the patients with manifested AIP are likely at higher risk. Only in one-third of the cases, HCC has coexisted with liver cirrhosis or well-known risk factors for HCC, such as viral hepatitis or heavy alcohol consumption.8,1315,85,89 Hepatoma should always be considered if a patient develops acute attacks or an abdominal pain after long-term remission or abnormally high porphyrin excretion pattern even at the old age.1315 Hepatomas can be solitary or multiple in AIP patients,13,91 and should be treated according to current guidelines (ie, hepatic resection, local ablation therapies, multikinase inhibitors) whenever possible.13,15,92
Since 10% of the patients with AIP die of hepatoma,91 the patients with AIP most likely benefit from regular screening for HCC after 50 years of age.1315 Early diagnosis of HCC is crucial for the prognosis and can be achieved only by accurate radiological imaging.
Among AIP patients with recurrent acute attacks, chronic neuropathic, myalgic, or abdominal pain usually accompanied by fatigue is common (18%22%).3,17 This could be due to repetitive autonomic and peripheral nerve damage during acute attacks, and the long-term hypocaloric nutrition inducing catabolic stage and muscle atrophy. The mouse model of AIP, which is in contrast to human autosomal-dominant AIP caused by compound heterozygous mutations in HMBS gene (HMBS -/-) and severe deficiency of HMBS enzyme, has developed chronic axonal motor neuropathy even in the absence of acute attacks and elevated ALA levels.19 In humans, a homozygous AIP patient has developed a chronic sensorimotor neuropathy associated with severe neurodegenerative encephalopathy and mental retardation at his early childhood but no chronic pain syndrome has been present.93
The treatment options include prevention of acute attacks as described earlier and prolonged treatment with gabapentin94 or antidepressants, such as fluoxetine.49 Prophylactic heme infusions commonly alleviate the chronic pain syndrome.3,49 Regular use of opiates induces tolerance to these drugs and high doses may increase the risk of side effects such as addiction, somnolence, and apnea.
rh-HMBS preparation has been shown to lower plasma PBG levels in symptom-free patients with increased excretion of urinary PBG.23 The similar biochemical effect of rh-HMBS therapy was demonstrated in theHMBS (/) mouse model.95 The rh-HMBS-enzyme replacement therapy, however, had no effect on the patients symptoms during acute attacks mainly due to constantly high plasma ALA levels.23 This may be due to the fact that the rh-HMBS included only the erythroid specific form of the enzyme and was not targeted to the liver, the main site of ALA overproduction. The potential development of rh-HMBS-enzyme replacement therapy should be focused on the delivery of an active enzyme into the liver restoring the normal HMBS activity and heme biosynthesis.
Both adenoviral-mediated and nonviral HMBS gene transfers corrected the metabolic defect in the cell lines of AIP patients and HMBS (/) mice.9698 Only virus-mediated DNA transfer into the liver was successful and corrected metabolic defect in HMBS (/) mice at least for a month.96,99 Adenoviral cytotoxicity, especially, for hepatocytes, the immunological response to viral antigens, and only transient transduction of the therapeutic gene limit potential applications of this method.100 Adeno-associated viral (AAV) vector encoding HMBS and driven by liver-specific regulatory elements, such as α1-microglobulin enhancer and α1-antitrypsin promoter, is a promising alternative to the first-generation adenoviral vectors, since it demonstrated long-term transgene expression of HMBS in the liver with reduced risk of side effects.101AAV vector encoding HMBS (recombinant AAV serotype 5-codon-optimized human HMBS, rAAV5-cohHMBS) has been used in macaques.102 The safety and efficiency of AAV vector containing the HMBSgene is currently investigated in the clinical trial (Phase I).103
Small interfering RNA targeting liver ALA synthase results in reduction of ALA synthase mRNA and prevents acute attacks in AIP mouse model, and it is under development for human studies.104 This demonstrates that downregulation of liver heme biosynthesis via direct ALA synthase inhibitor could result in a promising future therapy.
Before the glucose and hematin treatment of an acute attack has been introduced, the mortality rate during an acute attack of AIP was up to 66%.105 Currently, the improved diagnostics, the early and effective treatment with heme preparations, and the prevention of acute attacks have decreased the mortality substantially. However, the morbidity and mortality (5%20%) of an acute attack is still significant if the diagnosis of AIP is delayed.3,8,10,11 Thus, it is important that AIP patients are treated in the experienced centers with facilities that enable monitoring of their clinical and biochemical profile.
Current options to prevent acute attack include patients and family doctor education and family screening forHMBS mutation carriers. In patients with recurrent attacks, ovarian suppression using hormonal interventions, prophylactic heme therapy, or liver transplantation should be considered to improve the prognosis and quality of their lives. Future therapies, such as enzyme or gene delivery, should demonstrate clinical efficiency and safety before they can be applied to the clinical use. In the long-term follow-up, impaired renal function and hypertension should be treated carefully, and screening for hepatomas should be considered after 50 years of age.
The authors have participated in clinical trials organized by Zymenex, Alnylam, Clinuvel, and Boehringer Ingelheim, and as speakers in seminars organized by Orphan Europe. The authors report no other conflicts of interest in this work.
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Patient Meeting Results
Wednesday - December 9, 2015 @ 12:37:07
Patient Meeting Results
The Patient Educational Meeting, that we held last weekend in conjunction with the ASH convention, was a huge success. We would like to thank the doctors who has presented on the Meeting in Orlando, FL as well as our long-term member Amy Chapman for helping us to organize it. Also, special thanks to everyone who attend with their families and friends. We hope all who attend had a good experience.
Watch the APF E-news for the announcements about the upcoming meetings. Make sure your membership is up to date, so you receive all news.
"Remember.Research is the key to your cure!"
10 Ways to be happy! Start 2016 off right
Monday - December 7, 2015 @ 10:30:00
1. Dont start with profundities. When I began my Happiness Project, I realized pretty quickly that, rather than jumping in with lengthy daily meditation or answering deep questions of self-identity, I should start with the basics, like going to sleep at a decent hour and not letting myself get too hungry. Science backs this up; these two factors have a big impact on happiness.
2.Dolet the sun go down on anger. I had always scrupulously aired every irritation as soon as possible, to make sure I vented all bad feelings before bedtime. Studies show, however, that the notion of anger catharsis is poppycock. Expressing anger related to minor, fleeting annoyances just amplifies bad feelings, while not expressing anger often allows it to dissipate.
3. Fake it till you feel it. Feelings follow actions. If Im feeling low, I deliberately act cheery, and I find myself actually feeling happier. If Im feeling angry at someone, I do something thoughtful for her and my feelings toward her soften. This strategy is uncannily effective.
4. Realize that anything worth doing is worth doing badly. Challenge and novelty are key elements of happiness. The brain is stimulated by surprise, and successfully dealing with an unexpected situation gives a powerful sense of satisfaction. People who do new thingslearn a game, travel to unfamiliar placesare happier than people who stick to familiar activities that they already do well. I often remind myself to Enjoy the fun of failure and tackle some daunting goal.
5. Dont treat the blues with a treat. Often the things I choose as treats arent good for me. The pleasure lasts a minute, but then feelings of guilt and loss of control and other negative consequences deepen the lousiness of the day. While its easy to think, Ill feel good after I have a few glasses of wineâ?¦a pint of ice creamâ?¦a cigaretteâ?¦a new pair of jeans, its worth pausing to ask whether this will truly make things better.
6. Buy some happiness. Our basic psychological needs include feeling loved, secure, and good at what we do. You also want to have a sense of control. Money doesnt automatically fill these requirements, but it sure can help. Ive learned to look for ways to spend money to stay in closer contact with my family and friends; to promote my health; to work more efficiently; to eliminate sources of irritation and marital conflict; to support important causes; and to have enlarging experiences. For example, when my sister got married, I splurged on a better digital camera. It was expensive, but it gave me a lot of happiness.
7. Dont insist on the best. There are two types of decision makers. Satisficers (yes, satisficers) make a decision once their criteria are met. When they find the hotel or the pasta sauce that has the qualities they want, theyre satisfied. Maximizers want to make the best possible decision. Even if they see a bicycle or a backpack that meets their requirements, they cant make a decision until theyve examined every option. Satisficers tend to be happier than maximizers. Maximizers expend more time and energy reaching decisions, and theyre often anxious about their choices. Sometimes good enough is good enough.
8. Exercise to boost energy. I knew, intellectually, that this worked, but how often have I told myself, Im just too tired to go to the gym? Exercise is one of the most dependable mood-boosters. Even a 10-minute walk can brighten my outlook.
9. Stop nagging. I knew my nagging wasnt working particularly well, but I figured that if I stopped, my husband would never do a thing around the house. Wrong. If anything, more work got done. Plus, I got a surprisingly big happiness boost from quitting nagging. I hadnt realized how shrewish and angry I had felt as a result of speaking like that. I replaced nagging with the following persuasive tools: wordless hints (for example, leaving a new lightbulb on the counter); using just one word (saying Milk! instead of talking on and on); not insisting that something be done on my schedule; and, most effective of all, doing a task myself. Why did I get to set the assignments?
10. Take action. Some people assume happiness is mostly a matter of inborn temperament: Youre born an Eeyore or a Tigger, and thats that. Although its true that genetics play a big role, about 40 percent of your happiness level is within your control. Taking time to reflect, and making conscious steps to make your life happier, really does work. So use these tips to start your own Happiness Project. I promise it wont take you a whole year.
"Remember.Research is the key to your cure!"
Ways to Improve Your Health
Friday - December 4, 2015 @ 10:30:00
WHO wants to be sick? At the very least, an illness is an inconvenience and an expense. You not only feel bad, but when you are sick, you may not be able to go to work or school, earn any money, or look after your family. You may even need someone to look after you, and you may have to pay for expensive medicines and treatment.
Well has it been said that Prevention is better than cure. Some illnesses cannot be avoided. Still, there is much you can do to slow down or even prevent the onset of illness. Consider five things that you can do today to get on the road to better health.
1 PRACTICE GOOD HYGIENE
According to the Mayo Clinic, one of the best ways to avoid getting sick and spreading illness is to wash your hands. One of the easiest ways to catch a cold or influenza is to rub your nose or your eyes when your hands have been contaminated by germs. Your best defense against such contamination is to wash your hands regularly. Good hygiene can also prevent the spread of more serious conditions, such as pneumonia and diarrheal diseases, which every year cause the death of over two million children under the age of five. Even the spread of deadly Ebola can be minimized by the simple habit of washing hands.
There are certain times when hand washing is particularly important to protect your own health and that of others. You should wash your hands:
After using the toilet.
After changing diapers or helping a child to use the toilet.
Before and after treating a wound or a cut.
Before and after being with someone who is sick.
Before preparing, serving, or eating food.
After sneezing, coughing, or blowing your nose.
After touching an animal or animal waste.
After handling garbage.
And do not take it for granted that you are cleaning your hands properly. Studies have shown that a large percentage of those who use public toilets do not wash their hands afterward or do not wash them correctly. How should you wash your hands?
Wet your hands in clean running water and apply soap.
Rub your hands together to make a lather, not forgetting to clean your nails, your thumbs, the backs of your hands, and between your fingers.
Keep rubbing for at least 20 seconds.
Rinse in clean running water.
Dry with a clean cloth or a paper towel.
Such measures are simple but can avert illness and save lives.
2 USE A SAFE WATER SUPPLY
Obtaining sufficient clean water for ones family is a regular chore in some countries. Yet, access to clean water can become a concern inany part of the world when a main supply that is usually good to drink becomes contaminated as a result of a flood, a storm, a pipe break, or some other issue. If water does not come from a safe source or is not stored correctly, it can cause parasite infestation, as well as cholera, life-threatening diarrhea, typhoid, hepatitis, and other infections. Unsafe drinking water is one of the causes of an estimated 1.7 billioncases of diarrheal disease every year.
There is much you can do to slow down or prevent the onset of illness
Cholera is most often contracted when a person drinks water or eats food that is contaminated with fecal matter from infected people. What steps can you take to protect yourself, even in the immediate aftermath of a disaster, from this and other types of water contamination?
Ensure that all your drinking waterincluding the water used for brushing teeth, making ice, washing food and dishes, or cookingcomes from a safe source, such as an adequately treated public supply or sealed bottles from a reputable firm.
If there is any possibility that your piped supply has been contaminated, boil your water before use or treat it with an appropriate chemical product.
When using chemicals, such as chlorine or water-purifying tablets, follow the makers directions carefully.
Use quality water filters, if available and affordable.
If no water-treatment products are available, add household bleach, eight drops per gallon of water (two drops per liter), mix well, and then let the water stand for 30 minutes before using it.
Always store treated water in clean, covered containers to protect it from possible recontamination.
Ensure that any vessel used to take water from your stored supply, such as a ladle, is clean.
Handle water containers with clean hands, and do not dip your hands or fingers into water used for drinking.
3 WATCH WHAT YOU EAT
Good health is impossible without good nutrition, and for good nutrition you need a healthy, balanced diet. You may need to consider your intake of salt, fats, and sugar, and you should watch your portion sizes. Include fruits and vegetables in your diet, and vary what you eat. Reading the packaging will help you to select whole-grain foods when buying bread, cereals, pasta, or rice. These are richer in nutrients and fiber than the alternatives made from refined grain. As for proteins, eat small and lean portions of meat and poultry and try to eat fish a couple of times a week, if possible. In some lands it is also possible to find protein-rich foods from vegetable sources.
If you eat too many sugars and solid fats, you risk becoming overweight. To minimize this risk, drink water instead of sweet beverages. Eat more fruit instead of sugary desserts. Limit your intake of solid fats from such items as sausages, meat, butter, cakes, cheese, and cookies. And instead of using solid fats for cooking, you may want to use healthier oils.
Too much salt, or sodium, in the diet can raise your blood pressure to an unhealthy level. If this is your problem, use the information on food packaging to keep your sodium intake low. Instead of salt, use herbs and spices to flavor your meals.
How much you eat can be as important as what you eat. So, while enjoying your food, do not keep eating after you are no longer hungry.
An issue tied to nutrition is the risk of food poisoning. Any food can poison you if it is not prepared and stored properly. Every year, 1 out of every 6 Americans falls sick from food poisoning. Most recover without lasting ill effects, but some die from it. What can you do to minimize the risk?
Vegetables grow in soil that may have been treated with manure, so wash these items carefully before preparing them.
Wash your hands, cutting board, utensils, dishes, and countertops with hot, soapy water before preparing each item.
To avoid cross-contamination, never put food on a surface or plate that was previously in contact with raw eggs, poultry, meat, or fish, without first washing that surface.
Cook until the food reaches the right temperature, and promptly refrigerate any perishable items that are not going to be eaten immediately.
Discard perishable items left at room temperature for more than two hours or one hour if air temperature exceeds 90 degrees Fahrenheit (32°C).
4 STAY PHYSICALLY ACTIVE
Regardless of your age, you need regular physical activity to stay in good shape. Many people today do not exercise enough. Why is exercise important? Staying physically active can help you to:
Sleep well.
Stay mobile.
Maintain strong bones and muscles.
Maintain or achieve a healthy weight.
Lower your risk of suffering from depression.
Lower your risk of premature death.
If you do not stay physically active, you are more likely to:
Suffer from heart disease.
Suffer from type 2 diabetes.
Develop high blood pressure.
Develop high cholesterol.
Suffer a stroke.
The kind of physical activity that is right for you depends on your age and your health, so it would be wise to consult your doctor before beginning any new exercise program. According to various recommendations, children and adolescents should get at least 60 minutes of moderate-to-vigorous activity every day. Adults should get 150 minutes of moderate activity or 75 minutes of vigorous activity every week.
Choose an activity that is fun. You might consider basketball, tennis, soccer, brisk walking, cycling, gardening, chopping wood, swimming, canoeing, jogging, or other aerobic exercise. How can you tell whether an activity is moderate or vigorous? A general guide would be that moderate activity makes you sweat, but more vigorous exercise makes it hard for you to hold a conversation while doing it.
5 GET ENOUGH SLEEP
The amount of sleep needed varies from person to person. Most newborns sleep for 16 to 18 hours a day, toddlers about 14 hours, and preschoolers about 11 or 12. School-age children generally need at least 10 hours of sleep, adolescents perhaps 9 or 10, and adults from 7 to 8.
Getting the right amount of rest should not be considered optional. According to experts, sufficient sleep is important for:
Growth and development in children and teenagers.
Learning and retention of new information.
Maintaining the right balance of hormones that impact metabolism and weight.
Cardiovascular health.
Disease prevention.
Insufficient sleep has been linked to obesity, depression, heart disease, diabetes, and tragic accidents. Surely these give us good reason to want to get enough rest.
So, what can you do if you realize that you have a problem getting enough sleep?
Try to go to bed and get up at the same time every day.
Make your bedroom quiet, dark, relaxing, and neither too warm nor too cold.
Do not watch TV or use gadgets while in bed.
Make your bed as comfortable as possible.
Avoid heavy meals, caffeine, and alcohol before bedtime.
If after applying these suggestions you still suffer from insomnia or other sleep disorderssuch as excessive daytime sleepiness or gasping for breath while sleepingyou may want to consult a qualified health-care professional.
"Remember.Research is the key to your cure!"
What You Should Know About Mental Disorders
Wednesday - December 2, 2015 @ 17:10:21
I felt as though I had my breath knocked out of me, says Claudia, who had just been told she had bipolar disorder and post-traumatic stress disorder. Dealing with the stigma of a mental illness seemed overwhelming.
It took a long time to come to terms with our situation, says Claudias husband, Mark. But I realized that I had to focus on supporting my wife.
IF YOU or someone you love were diagnosed with a mental disorder, how would you feel? Thankfully, mental illness can be treated. Let us examine a few things you should know that will give you a better understanding of mental disorders.*
Key Facts About Mental Health
Mental disorders afflict hundreds of millions of people in every part of the world and impact on the lives of their loved ones. One in four people will be affected by mental disorder at some point in their lives. Depression is the single largest contributor to worldwide disability. Schizophrenia and bipolar disorder are among the most severe and disabling disorders. . . . Although huge numbers of people are affected, mental disorders remain hidden, neglected and discriminated against.World Health Organization (WHO).
According to WHO, many people with mental illness refrain from seeking treatment because of the stigma associated with it.
Although most mental disorders are treatable, in the United States approximately 60 percent of adults and almost 50 percent of youths aged 8 to 15 with a mental disorder did not receive treatment in the past year, reports the National Alliance on Mental Illness.
Understanding Mental Disorders
What is mental illness? Experts define a mental disorder as a significant dysfunction in a persons thinking, emotional control, and behavior. The condition often disrupts a persons ability to relate to others and to deal with the demands of life.
Mental-health disorders are not the result of personal weakness or a character flaw
The severity of symptoms can vary in length and intensity, depending on the individual and the particular ailment and circumstances. It can affect people of any gender, age, culture, race, religion, or educational and income level. Mental-health disorders are not the result of personal weakness or a character flaw. Through appropriate medical care, individuals can be treated and can live a productive and fulfilling life.
Treating Mental Disorders
Mental-health professionals can treat many mental-health disorders successfully. The first crucial step, then, is to obtain a thorough assessment from a competent health professional who is experienced in treating mental conditions.
Sufferers, however, can benefit from such experience only when they accept suitable treatment. This may require overcoming any reluctance to talk to others about a mental illness. Treatment may include talking to trained mental-health professionals who can help them understand their illness, resolve practical problems, and reinforce the need not to give up the treatment. At such consultations, a family member or friend can play a vital role by providing reassurance and support.
Many people have learned to deal with mental disorders after acquiring a better understanding of their condition and following the treatment prescribed by mental-health professionals. Before my wife was diagnosed, says Mark, quoted earlier, we had little understanding of mental illness. But weve learned to take life one step at a time and adapt to our situation. Over time, we have benefited from the support of reliable professionals as well as family and friends.
The first crucial step is to obtain a thorough medical assessment from a competent health professional
Claudia agrees. In the beginning, my diagnosis felt like a prison sentence, she admits. But even though my illness places limitations on both of us, I have learned that seemingly impossible hurdles can be overcome. So I cope with my mental illness by working together with my treatment team, nurturing relationships with others, and taking one moment at a time.
Spiritual Health Is Vital
The Bible does not indicate that spirituality cures medical problems. Still, many families around the world have derived much comfort and strength from what the Bible teaches. For instance, the Bible assures us that our loving Creator is keenly interested in consoling those who are brokenhearted and crushed in spirit.Psalm 34:18.
While the Bible is not a health-care book, it provides practical guidance that can help us to cope with painful emotions and distressing circumstances. The Bible can also give us hope for a future when life on earth will be free of illness and pain. Gods Word promises: At that time the eyes of the blind will be opened, and the ears of the deaf will be unstopped. At that time the lame will leap like the deer, and the tongue of the speechless will shout for joy.Isaiah 35:5, 6.
Upcoming Patient Educational Meeting
Thursday - December 3, 2015 @ 16:04:24
Upcoming Patient Educational Meeting
Date and Time: Sunday, December 6, 2015, 4:00 - 6:00 PM ET
* Presentations by World Renowned Porphyria Experts. We are expecting to have Dr. John Phillips, Dr. Charles Parker (University of Utah School of Medicine) and Dr. Samuel Silver (University of Michigan Medical School) present at the meeting.
* Opportunity to Participate in a Q & A Session.
* Meet Friends who Share Your Experiences with Porphyria.
* View the Latest Educational Material from the American Porphyria Fdn.
Location: Ramada Plaza Resort & Suites International Drive Orlando
I WOKE up one morning when I was 12 years old, remembers James,* sat on the edge of my bed, and wondered, Is today the day I die? James was in the grip of major depression. Every day of my life, says James 30 years later, I have fought this emotional and mental illness. James felt so worthless when he was young that he tore up his childhood photographs. I didnt even think that I was worth remembering, he recalls.
Because we all contend with feelings of sadness occasionally, we could conclude that we understand what depression is all about. But how does it feel to have clinical depression?
A Cruel Intruder
More than just a spell of melancholy blues, clinical depression is a grave disturbance that often hinders a person from carrying out daily activities.
For example, for more than 40 years, Ã?lvaro has been afflicted with fear, mental confusion, anguish, and deep sorrow. He explains: My depression made it difficult for me to deal with the opinions of others. I always felt responsible for everything that went wrong. He describes depression as having a terrible pain without knowing where the pain is located, fear without knowing why and, worst of all, absolutely no desire to talk about it. Now, though, he has found some relief. He knows the cause of his symptoms. He says, Knowing that others have the same problem that I have has made me feel better.
In Brazil, 49-year-old Maria was afflicted with depression that caused insomnia, pain, irritability, and a seemingly unending feeling of sadness. When her condition was first diagnosed, Maria was relieved to put a name to the cause of her suffering. But then I became more anxious, she explains, because so few people understand depression and it carries a stigma.
Nothing to Be Sad About?
Although depression sometimes has an obvious trigger, it often intrudes on a persons life without warning. Your life is suddenly darkened by a cloud of sadness for no apparent reason, explains Richard from South Africa. Nobody you know has died, and nothing distressing has occurred. Yet, you feel dejected and listless. And nothing will make the cloud go away. You are overwhelmed by feelings of despair, and you dont know why.
Depression is nothing to be ashamed of. Yet, Ana in Brazil felt ashamed to be diagnosed with depression. In fact, eight years later I still feel ashamed of myself, she admits. In particular, she finds it difficult to deal with her emotional anguish. The suffering is sometimes so intense, she explains, that I feel physical pain. All the muscles in my body hurt. At such times it is almost impossible to get out of bed. And then there are the times when Ana cannot stop crying. I sob with such intensity and become so exhausted, she says, that it feels as though my blood has stopped circulating.
Your life is suddenly darkened by a cloud of sadness for no apparent reason
The Bible acknowledges that people can become dangerously low in spirit. For instance, the apostle Pauls concern about one man was that he might be swallowed up by his being overly sad [swallowed up in overwhelming depression, Jewish New Testament]. (2 Corinthians 2:7) Some depressed people become so distraught that they wish they could just fall asleep in death. Many feel as did Jonah the prophet: My dying is better than my being alive.Jonah 4:3.
What can depressed ones do to treat and cope with this distressing malady?
"Remember.Research is the key to your cure!"
IMPORTANT EPP NOTICE LETTERS Take Action Now!
Thursday - November 26, 2015 @ 09:30:00
November 25, 2015
Dear EPP Family,
We are a volunteer team, working with the APF to secure your EPP patient experiences in letter-form so that we can take them collectively to the FDA to ask them for the accelerated approval of the drug Afamelanotide.
Your contributions to previous letter campaigns worked. They convinced the FDA to approve Phase III of the drug trials in the USA, and our American letters helped convince the European Medicines Agency to grant approval of the drug in the European Union. Now it is our turn to seek approval for Afamelanotide by the FDA in the USA!
Our goal is twofold: (1) to collect more than 300 letters from patients, family and friends by December 15, 2015 and (2) for all of us to reach out to our US Congress Representatives to ask for their help.
Enclosed please find an overview of the letter writing campaign with tips and instructions (who, what, why, where and when). In addition, there is a US Congressional Caucus called the Rare Disease Legislative Advocates (RDLA). You can ask your Congress Member to join. Simple instructions and an online link are also enclosed. It takes less than 5 minutes to complete the request online!
If you have any questions, please reach out to us or to the APF. Let's make this happen. Patient advocacy works. THANK YOU FOR PARTICIPATING!
AN EPP PATIENT LETTER WRITING CAMPAIGN TO THE FDA IS UNDERWAY
TO ASK THE FDA TO ACCELERATE THE APPROAVAL FOR AFAMELANOTIDE
WHO
·You (Erythropoietic Protoporphyria patients), your family and your friends ·Please note that this is a patient-driven letter writing campaign as we are acting independently of the drug company
WHAT
·We need to collect as many patient EPP experiences as possible addressed to the Director at the Center for Drug Evaluation and Research at the FDA's Division of Dermatology (See enclosed letter template) ·You may also wish to send a copy of your letter to your US Congress Representative and Senators in Washington DC. Please look them up through this link and add their names to the cc list at the end of your letter. We will ensure a copy is sent to them.https://www.opencongress.org/people/zipcodelookup ·Once we collect all your letters, the APF will deliver the full stack of letters, in person, to the FDA and ask for the accelerated approval for Afamelanotide (This meeting is likely to happen in January 2016) ·We ask that each patient with EPP commit to providing at least 3 letters (from yourself and at least 2 others; of course, more than 3 letters is most welcome) ·Parents of EPP children, we especially encourage the children to participate and write letters
Tips for Patient Letters:
oPlease ask for the FDA to accelerate the approval for Afamelanotide
oPlease focus your letters on 4 topics that we know the FDA is keen to understand the most. These are topics that only, us patients, can tell: How EPP affects your ability (1) to attend school and/or (2) work and/or (3) complete everyday tasks as well as (4) your experience during the drug trials, if applicable
oAlthough EPP skin reactions are not always visible, if you have photos that demonstrate swelling, scarring, scabbing etc., please include them with your letters
Tips for Friends and Family Letters:
oPlease ask for the FDA to accelerate the approval for Afamelanotide
oPlease focus your letters on your observations of how EPP affects your friend or family member, how hard it is for him/her (the EPP patient) and even how it effects him/her as well as how it affects you and/or your family
WHY
·Patient advocacy works ·We believe that our advocacy is critical to ensure approval of the drug ·Independent of the drug company, it is important that we demonstrate why we need this drug
WHERE
·Do NOT send your letters directly to the FDA ·SEND LETTERS TO THE APF:
(1)The American Porphyria Foundation, 4900 Woodway, Suite 780, Houston, TX 77056
·Send a signed hard copy by mail to the APF OR scan your signed letter and email it electronically to the APF ·ALL LETTERS MUST HAVE THE AUTHOR'S SIGNATURE, NAME AND ADDRESS
WHEN
·Please provide letters to the APF by December 15, 2015
* * * * *
Letter Template
[Insert Date]
Kendall Marcus, M.D.
Director, Division of Dermatology and Dental Products
Center for Drug Evaluation and Research
Food and Drug Administration
White Oak Campus, WO 22/Rm. 5202
10903 New Hampshire Avenue
Silver Spring, MD 20993
Dear Dr. Marcus:
[Insert your letter here]
Sincerely,
[Your signature here]
[Insert your name here]
Age, [insert] years old
[Insert your address here:
# Street
Town, State Zip Code]
[EPP patients, please cc your one US Congress Representative and your two US Senators, e.g.:
cc: The Honorable Cory Booker (D-NJ, United States Senate), The Honorable Bob Menendez (D-NJ, United States Senate), The Honorable Rodney Frelinghuysen (R-NJ, 11th District, United States Congress)]
THE RARE DISEASE LEGISLATIVE ADVOCATES OF THE US CONGRESS
An excerpt from the RDLA's website:
Rare Disease Legislative Advocates (RDLA) is a collaborative organization designed to support the advocacy of all rare disease groups. Our goal is to empower the patient to become an advocate! By growing the patient advocacy community & working collectively we can amplify our many voices to ensure rare disease patients are heard in State & Federal Government.
As an advocate for patients with rare diseases you are a very important part of the legislative process. You can make the difference as you are the voices your legislators and congressmen want, or in some cases do not want to hear. Please complete the form via the link below and contact your Member of Congress to ask them to join the RDLA.
EPP Patients:
The RDLA has made it simple for you to send your Congress Member an email letter request. All you need to do is copy and paste this link into your online browser to go to their website form. Then input your name and address. Your Congress Member's details will automatically populate a letter request and you will be able to insert a few sentences about yourself and EPP and send the email:
Notice: You will send the original letter to the APF and send a copy to your Congressmen.
Thank you
"Remember.Research is the key to your cure!"
Public Service Announcement American Porphyria Foundation
Wednesday - November 25, 2015 @ 10:30:00
We hope that you will enjoy this wonderful day with good health in mind. We thank you for all of your support and will continue to bring you new research and information about EPP Drug approval and Acute Porphyria Studies starting soon. If you have any questions please feel free to contact the APF 1-866-APF-3635. We thank you again for your continued support. Stay Happy & Well. APF Staff & Volunteers
"Remember.Research is the key to your cure!"
Shadow Race in Vernon, TX was a success!
Friday - November 20, 2015 @ 10:30:01
Shadow Race in Vernon, TX was a success!
The Cook Family: "Thank you to all of the sponsors for the 1st Annual Shadow Race in Vernon, Texas! We cannot thank you enough for the support in raising awareness for Porphyria. In our 1st annual race we were able to collect monetary donations, totaling $5000 for the "added money". Also donated were items such as custom made buckles, custom made spur straps, Total Equine Feed, head stalls, hay bags, rope halters, and other horse maintenance supplies. Pizza, candy, homemade cinnamon rolls, and drinks were donated for the concession stand and t-shirts were sold. In all we were able to donate $4000 to the American Porphyria Foundation and pay out $11,600 to the winners! A huge thank you to all that supported and or donated! We look forward to the 2nd Annual Shadow Race in 2016 and hope you will consider giving again!"
Cason and Caul, brothers with EPP.
From NCBI CYP2D6 Polymorphisms in Patients with Porphyria PCT Type
The cytochrome P-450 (CYP) isoenzymes, a superfamily of heme proteins which are the terminal oxidases of the mixed function oxidases system, metabolize more than 70% of all clinically approved drugs. The highly polymorphic CYP2D6 isoform metabolizes more than 25% of most common drugs, and the phenotypes of the 70-plus allelic variants range from compromised to excessive enzymatic activity. Porphyrias are a group of inherited or acquired metabolic disorders of heme biosynthesis, due to a specific decrease in the activity of one of the enzymes of the heme pathway. Clinical signs and symptoms of porphyrias are frequently associated with exposure to precipitating agents, including clinically approved drugs. CYP enzymes, including CYP2D6, participate in the metabolism of some porphyrinogenic drugs, leading to the deregulation of heme biosynthesis. Considering that some of the drugs not recommended for use in porphyric patients are metabolized by CYP2D6, the presence of CYP2D6 polymorphisms in porphyric patients would influence the triggering of the disease when these individuals receive a precipitating agent that is metabolized by CYP2D6. To investigate CYP2D6 polymorphisms in porphyric patients, healthy Argentinean volunteers, porphyric patients, and a group of individuals with high levels of iron were studied. Results indicated that the CYP2D6*3 and CYP2D6*4 alleles, in particular, would be linked to the onset of disease. Predictive genotyping for CYP2D6 in porphyric patients holds promise as a method to improve the clinical efficacy of drug therapy and to personalize drug administration for these patients.
The cytochrome P-450 (CYP) isoenzymes are a superfamily of heme proteins which are the terminal oxidases of the mixed-function oxidase system (1). The 1 to 3 families of CYP are responsible for 70% to 80% of all phase Idependent metabolism of clinically used drugs (2). CYP2D6 isoform metabolizes more than 25% of most common drugs, including antiarrhythmics, antidepressants, beta blockers, neuroleptics, and opioids (3). CYP2D6 gene is extremely polymorphic, and more than 70 allelic variants have been described (4,5); as a result, metabolism and excretion rates of drugs vary between individuals, from extremely slow to ultra-fast. Different phenotypes can be distinguished: poor metabolizers (PM) lack the functional enzyme; intermediate metabolizers (IM) carry 2 different alleles, leading to partial activity; efficient metabolizers (EM) have 2 normal alleles; efficient intermediate metabolizers (EIM) are heterozygous for 1 deficient allele; and ultra-rapid metabolizers (UM) have multiple gene copies (6). The clinical consequences of genetic polymorphisms in drug metabolism depend on whether the activity of the drug lies with the substrate or its metabolite, as well as the extent to which the affected pathway contributes to the overall elimination of the drug (1). For example, the mutant CYP2D6*3 (CYP2D6A) allele with the A2637 deletion in exon 5 and the mutant CYP2D6*4 (CYP2D6B) allele with a G1934A splice site defect are among the most common mutations. These mutations result in decreased or lack of CYP2D6 isoenzyme activity, leading to PM phenotype (79). PM individuals have an increased risk for adverse side effects or therapeutic failure following drug treatment.
Porphyrias are a group of inherited or acquired metabolic disorders of heme biosynthesis in which specific patterns of overproduction of heme precursors are associated with characteristic clinical features. Each type of porphyria is the result of a specific decrease in the activity of one of the enzymes of the heme pathway (1012). Porphyrias are classified as acute, cutaneous, or mixed according to clinical features. Acute attacks characteristic of acute intermittent porphyria (AIP) and variegate porphyria (VP), both hereditary, are often triggered by exposure to exogenous precipitating factors (13) including a wide range of commonly prescribed drugs. There are two main forms of porphyria cutanea tarda (PCT): type I (sporadic or acquired) and type II (familial or hereditary) in which the enzyme activity of uroporphyrinogen decarboxylase (URO-D) is reduced to approximately 50% of normal in all tissues. In type I PCT, subnormal URO-D activity is restricted to the liver. There is also a form of familial PCT called type III, in which a family history of PCT is observed, but subnormal URO-D activity is restricted to the liver. No mutations have been found in the URO-D gene in types I and III. PCT triggering is frequently associated with exposure to precipitating agents, such as polyhalogenated aromatic hydrocarbons, alcohol abuse, estrogen ingestion, iron overload, and infections (14).
CYP enzymes participate in the metabolism of some porphyrinogenic drugs, leading to the deregulation of heme biosynthesis, which would influence the pathogenesis of porphyrias. Considering that some of the drugs not recommended for use in porphyric patients are metabolized by CYP2D6, inheritance of polymorphic CYP2D6 metabolizing genes would be an important determinant of individual variation in acute symptoms. Moreover, the presence of CYP2D6 polymorphisms in porphyric patients with genetic or biochemical alterations in any of the enzymes of the heme pathway would influence the triggering of the disease when these individuals received a precipitating agent that was metabolized by CYP2D6. The aim of this work was to investigate CYP2D6 polymorphisms in porphyric patients. To this end, CYP2D6*3 and CYP2D6*4 alleles were studied in healthy volunteers, porphyric patients, and a group of individuals with high levels of iron.
All primers used for PCR analysis were synthesized by Fagos Laboratory (Buenos Aires, Argentina). All other chemicals and reagents were of molecular grade from Merck, Sigma, Promega, Ambion, Bio Labs and Amersham; Taq DNA polymerase was from Invitrogen. Digestion enzymes were from Bio Labs.
Subjects
A total of 120 subjects51 healthy volunteers, 50 porphyric patients, and 19 individuals with high iron levelswere included in the study, all of Caucasian origin. The porphyric patient group (Table 1), previously studied in the Centro de Investigaciones sobre Porfirinas y Porfirias, consisted of 20 individuals diagnosed with AIP, 15 with PCT, and 15 with VP. All patients were diagnosed biochemically and genetically except 3 PCT individuals who were diagnosed only biochemically. All the individuals with high iron levels were normal for mutations in HFE gene responsible for hereditary hemochromatosis type I. All subjects gave their informed consent to participate in this study.
Genomic DNA was extracted from EDTA-collected whole blood samples using the GFX Genomic Blood DNA Purification Kit (Amersham). Target DNA (0.51 μg) was amplified by PCR as described by Daly et al. (15) with slight modifications. CYP2D6*3 and CYP2D6*4 alleles were detected by amplification of the region of interest using primers G1 (bp 18271846; 5�-TGCCGCCTTCGCCAA CCACT-3�) and B1 (bp 26382657; 5�-GGCTGGGTCCCAGGTCATAC-3�). The reaction was carried out in a total volume of 50 μl containing 14 mM Tris-HCl, pH 8.3, 2 mM MgCl2, 5% dimethyl sulfoxide with 0.2 mM dTNPs, 0.52 μM primers, and 2.5 units Taq DNA polymerase. For amplification, 30 cycles were carried out of 1 min at 95 °C, 1 min at 62 °C, and 3 min at 70 °C in a PTC 100 Research Mini Cycle thermocycler. The product (25 μL) was digested with 12.5 units of BsaAI and 15 units of BstNI restriction enzymes, at 50 °C for 3 h. To control the digestion by BsaAI, GADPH gene, amplified by separate PCR reaction, was added to the CYP2D6 digestion. The GAPDH PCR was carried out using the primers R4 (5�-AGAAACAGGAGGTCCCTACT-3�) and R5 (5�-GTCGGGTCAACGCTA GGCTG-3�) and similar conditions to those for CYP2D6 amplification. The digest was analyzed on a 8% polyacrylamide gel using 1% TBE as the buffer, and the gel was stained with ethidium bromide.
Statistical analysis
Data were analyzed using Ï?2 test. P < 0.05 was considered significant.
Figure 1 shows representative band patterns found for wild-type and CYP2D6*3 and CYP2D6*4 mutant variants of CYP2D6 gene in all the subjects analyzed. Between 3 and 6 bands for mutant and wild-type variants were observed. One of these bands was distinctive for CYP2D6*3 (160 bp) and the other was distinctive for CYP2D6*4 (388 bp). wt/wt pattern showed 4 bands (280, 168, 139, and 109 bp). In the case of wt/*3 or wt/*4, bands of 160 bp and 388 bp appeared, respectively. *3/*3 pattern presented the band of 160 bp but not the corresponding band of 168 bp; in *4/*4 pattern, the band of 388 bp was present while the bands of 109 bp and 280 bp were absent. *3/*4 individuals presented both bands of 160 bp and 388 bp. The bands of 500 bp corresponded to GAPDH gene.
Representative band patterns of CYP2D6*3 and CYP2D6*4 alleles. Band pattern observed for the wild-type (wt/wt ), heterozygous (*3/wt, *4/wt ), compound heterozygous (*3/*4), and homozygous (*3/*3, *4/*4) CYP2D6 alleles. M indicates marker of 100 bp. Lanes
Genotype distribution of CYP2D6 alleles among healthy subjects and porphyric patients is shown in Table 2. In the control group, 5.8% (3 of 51) were heterozygous for CYP2D6*3 and 33.3% (17 of 51) for CYP2D6*4 allele; 1 of 51 (1.9%) was homozygous for CYP2D6*3 and CYP2D6*4. In the PCT group, 26.6% (4 of 15) were heterozygous for CYP2D6*4 and 1 of 15 (6.6%) was homozygous for this allele. In the AIP group, 10% (2 of 20) were heterozygous for CYP2D6*4. In the VP group, 26.6% (4 of 15) were heterozygous for CYP2D6*4, and 1 of 15 (6.6%) was double heterozygous (both CYP2D6*3 and CYP2D6*4). In individuals with high levels of iron, 15.7% (3 of 19) were heterozygous for CYP2D6*4; the same percentage were homozygous, significantly different from the control group (P < 0.05). None of the patients with porphyria or high iron was found to be homozygous for CYP2D6*3.
The frequency of CYP2D6 alleles observed is shown in Table 3. In the control group, 4.9% of alleles (5 of 102) were CYP2D6*3 and 18.6% (19 of 102) were CYP2D6*4. The PCT group showed a frequency of 20% (6 of 30) CYP2D6*4. In the AIP group only 5% (2 of 40) were CYP2D6*4 (P < 0.05); in the VP group, the frequency of this allele was 16.6% (5 of 30). The PV group showed a frequency of 3.3% (1 of 30) CYP2D6*3. In individuals with high levels of iron, CYP2D6*4 frequency was 23.6% (9 of 38). Results obtained for the PCT, PV, and high iron groups were no different from the control group.
The predicted phenotype distribution is shown in Table 4. The phenotype was predicted according to the genotypes as follows: EM carried 2 CYP2D6 wild-type alleles, EIM carried 1 deficiency and 1 wild-type allele, and PM were homozygous for 2 deficiency alleles. In the control group, 56.9% were identified as EM, 39.1% as EIM, and 3.9% as PM. In the AIP group, 90% were classified as EM and 10% as EIM. In the PCT and VP group, 66.8% were classified as EM, 26.6% as EIM, and 6.6% as PM. In the group with high levels of iron, 68.6% were identified as EM and 15.7% as EIM and PM.
CYP2D6 is one of the most studied polymorphic genes, and its clinical relevance and allelic frequency have been extensively investigated in different ethnic groups (16,17). To date, no data in the Argentinean population or in porphyric individuals worldwide have been reported. Our results showed a frequency of 18.6% CYP2D6*4 allele in the healthy group. The frequency of this allele was similar to that reported for other Caucasian populations (8,18,19). The CYP2D6*3 frequency found in our study (4.9%) was slightly higher than others (9,20,21).
The analysis of predicted phenotype distribution showed a difference in the frequency of CYP2D6*3 and CYP2D6*4 alleles between the control group and porphyric patients. When the results obtained in all porphyric patients studied were analyzed, the frequency of EM phenotype was higher (P < 0.05) than in healthy controls. When each type of porphyria was analyzed separately, only the EM phenotype in the AIP group was significantly higher than the healthy group. These results indicate that polymorphisms in porphyric patients might also have a significant influence on the individual susceptibility to foreign substances and the triggering of this disease. EM would be more exposed than EIM and PM to genotoxic porphyrinogenic xenobiotic metabolites. Several authors have presented similar results in different studies performed with lung cancer and urinary bladder cancer patients (2224). Agündez et al. (25) observed a significant correlation between EM and the risk of liver cancer development.
In this study, the CYP2D6 polymorphism was also investigated in nonporphyric individuals presenting with some hepatic alterations and high levels of iron. A higher percentage of this polymorphism was found in these subjects than in the control group. These individuals would be particularly exposed for an extended time period to the possible toxic effects of unmetabolized chemicals. These findings are in agreement with other studies that revealed an association between PM and breast cancer or leukemia (2628).
Gardlo et al. (29) analyzed the CYP1A1 and CYP1A2 polymorphism prevalence in patients with PCT and suggested that the m4 polymorphism in Caucasian PCT type II patients might contribute to a higher susceptibility to porphyrinogenic compounds. In a similar study, Christiansen et al. (30) reported that the A/A genotype of CYP1A2 occurred significantly more often in PCT compared with the healthy control group in a Danish population.
In this study, we observed that, in the AIP group, no presence of polymorphisms was found among the 6 symptomatic patients, although 2 men with latent AIP were heterozygous for CYP2D6*4. In patients with VP, only 1 of the 7 individuals with latent VP carried the polymorphism CYP2D6*4 in the heterozygotic state. In the symptomatic VP cohort, 3 of 8 individuals possessed a heterozygous *4 allele, only 1 of whom had undergone an acute attack, while the other 2 presented only cutaneous manifestations. One woman in this group carried both polymorphisms (*3/*4). In the PCT group, among 8 individuals with hereditary PCT, 3 were heterozygous for CYP2D6*4: 1 was latent PCT; among the 3 patients with acquired PCT, 1 was heterozygous for CYP2D6*4 and another carried the same allele in the homozygous form.
Results presented here, although preliminary, demonstrated for the first time that 13% of porphyric subjects analyzed carried the CYP2D6*4 allele and only 1% carried the CYP2D6*3 allele. However, further studies in greater cohorts should be analyzed to provide a clearer picture of the extent and correlation of mutant genotypes in porphyric patients compared with healthy controls. Also, other genotyping studies should be performed for detecting the presence of other mutant alleles in these individuals, such as CYP2D6D which, like CYP2D6*3 and CYP2D6*4, is among the most common mutations leading to PM phenotype in the Caucasian population.
The information obtained with this research would have an impact on the practice of medicine in the near future. Many authors (6,21,31) have already determined that genotyping P450 would be a useful tool to predict the pharmacogenicity of drugs. Currently, CYP2D6 polymorphisms cause interindividual variability in drug response, influencing the treatment of several diseases (4,6). In the case of porphyrias, some drugs have shown conflicting evidence about their porphyrinogenicity in some individuals. Predictive genotyping for CYP2D6 in porphyric patients holds promise as a method to improve the clinical efficacy of drug therapy and to personalize drug administration for these patients.
A.M. Buzaleh, V.E. Parera, and A. Batlle hold the post of Associated, Independent and Superior Scientific Researchers at the Argentine National Research Council (CONICET). J. Lavandera is a fellow from the Argentine Scientific and Technologic Agency (ASTA). This work has been supported by grants from the CONICET, the ASTA, and the University of Buenos Aires, Argentina. We wish to acknowledge Dr. M.V. Rossetti for her counseling in the optimization of the techniques used in this work.
1. Chang GWM, Kam PCA. The physiological and pharmacological roles of cytochrome P450 isoenzymes.Anaesthesia. 1999;54:4250. [PubMed]
2. Ingelman-Sundberg M. The human genome project and novel aspects of cytochrome P450 research.Toxicol Appl Pharmacol. 2005;207:S526. [PubMed]
3. Burroughs VJ, Maxey RW, Levy RA. Racial and ethnic differences in response to medicines: toward individualized pharmaceutical treatment. J Natl Med Assoc. 2002;94:126. [PMC free article][PubMed]
4. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005;5:613. [PubMed]
5. Scordo MA, Caputi AP, DArrigo C, Fava G, Spina E. Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res. 2004;50:195200. [PubMed]
6. Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci. 2004;25:193200. [PubMed]
7. Saxena R, et al. Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with poor metabolizer phenotype. Hum Mol Gen. 1994;3:9236. [PubMed]
8. Sachse C, Brockmoller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet. 1997;60:28495. [PMC free article][PubMed]
9. van Der Weide J, Steijns L. Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem. 1999;36:7229. [PubMed]
11. Nordmann Y, Puy H, Deybach JC. The porphyrias. J Hepatol. 1999;30:126. [PubMed]
12. Thadani H, Deacon A, Peters T. Diagnosis and management of porphyria. Br Med J. 2000;320:164751.[PMC free article][PubMed]
13. Meyer UA, Schuurmans MM, Lindberg RL. A review of the pathogenesis of the neurological manifestations of the acute porphyrias. Semin Liver Dis. 1998;18:4352. [PubMed]
15. Daly AK, Steen VM, Fairbrother KS, Idle JR. (1996) CYP2D6 Multiallelism. In: Methods in Enzymology: Cytochrome P450. Waterman MR, Johnson EF (eds.) Academic Press, vol. 272, chapter 22, p. 199211.
16. Lennard MS. Genetic polymorphism of sparteine/debrisoquine oxidation: a reappraisal. Pharmacol Toxicol. 1990;67:27383. [PubMed]
17. Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 2002;53:11122. [PMC free article][PubMed]
18. Marez D, et al. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics.1997;7:193202. [PubMed]
19. Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3:22943. [PubMed]
20. Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol. 1997;37:26996. [PubMed]
21. Cascorbi I. Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication. Eur J Clin Invest. 2003;33:1722. [PubMed]
22. Caporaso N, Landi MT, Vineis P. Relevance of metabolic polymorphisms to human carcinogenesis: evaluation of epidemiologic evidence. Pharmacogenetics. 1991;1:419. [PubMed]
23. Agündez JA, et al. Debrisoquin oxidation genotype and susceptibility to lung cancer. Clin Pharmacol Ther. 1994;55:104. [PubMed]
24. Anwar WA, Abdel-Rahman SZ, El-Zein RA, Mostafa HM, Au WW. Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients. Carcinogenesis. 1996;17:19239.[PubMed]
25. Agündez JA, Ledesma MC, Benitez JM, Ladero JM, Rodriguez-Lescure A, Diaz-Rubio E, Diaz-Rubio M. CYP2D6 genes and risk of liver cancer. Lancet. 1995;345:8301. [PubMed]
26. Wolf CR, et al. Relationship between the debrisoquine hydroxylase polymorphism and cancer susceptibility. Carcinogenesis. 1992;13:10358. [PubMed]
27. Anthony LB, Thomas JB, Hande KR. Cytochrome P-450IID6 phenotyping in cancer patients: debrisoquine and dextromethorphan as probes. Cancer Chemother Pharmacol. 1995;36:1258. [PubMed]
28. Topic E, Stefanovic M, Ivanisevic AM, Petrinovic R, Curcic I. The cytochrome P450 2D6 (CYP2D6) gene polymorphism among breast and head and neck cancer patients. Clin Chim Acta. 2000;296:1019.[PubMed]
29. Gardlo K, Selimovic D, Bolsen K, Ruzicka T, Abel J, Fritsch C. Cytochrome P4501A1 polymorphisms in a Caucasian population with porphyria. Exp Dermatol. 2003;12:8438. [PubMed]
30. Christiansen L, Bygum A, Jensen A, Thomsen K, Brandrup F, Horder M, Petersen NE. Association between CYP1A2 polymorphism and susceptibility to porphyria cutanea tarda. Hum Genet. 2000;107:6124. [PubMed]
31. Spear B, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trend Mol Med.2001;7:2014. [PubMed]
Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ
"Remember.Research is the key to your cure!"
FULL SPEED AHEAD EPP
Wednesday - November 18, 2015 @ 10:30:02
FULL SPEED AHEAD
The APF and our FDA Committee will be leading a FULL SPEED AHEAD charge to gain FDA accelerated approval of Afamelanotide/SCENESSE, the new treatment for EPP.
This treatment was so revolutionary that some of our friends are flying to Switzerland for the treatment. This is outrageous that our own citizens are not being given a treatment that is available to half of the world. Instead, we must raise funds to travel to Europe for this treatment . It is time for us to act.
The APF cannot do this without YOU, but we firmly believe with your help we will see FDA approval. YOU will be hearing from committee members about what each of YOU can do.
Many of YOU have sent letters to the FDA via the APF and we thank you heartily for those letters. However, we need many, many more letters describing your personal experience and need for a treatment. Those who were fortunate to have received the real treatment during the clinical trials should include your experience in your letter.
YOU can also contact your legislators or better yet, the APF will address a letter to your Congressman to include with your personal letter.
We are now working full speed ahead. Watch for the APF Advocacy committee members to answer your questions and encourage you to write your letters and contact your congressmen.
So I took it the next step and contacted the company that interprets results from 23andme.com with a company called LivewellO.com. For around twenty dollars they can interpret some results. My question through email took 3 attempts with no phone number to contact them by.
My question was this:
Hello my name is Amy Chapman with the American
Porphyria foundation. We have been asked by 23andme to ask some specific questions. Porphyria is a group of rare metobolic disease. The only way to get a clear diagnosis is through genetic DNA testing. Genetic testing is very expensive and takes some time to get results. Many of the patients have been using your services for a diagnosis and that is impossible to do first how do you explain this in particular to a diagnosis of porphyria which also depending on deficient enzyme are 8 different types.
Since porphyria is rare how do you say that you can diagnose these ppl many have been to world porphyria experts spent 30 plus yrs in porphyria relations in genetics many have been tested and do not meet the criteria set by FDA standards and then they come to you and say they have it only to believe they do and the medications used and cost can be considered close to high drug costs 30 k or more for a daily dose but they have been told they do not have the disease by genetic experts. So please explain what you do how you do and can you actually diagnosis such a rare disease called porphyria?? Please respond urgently
Sincerely,
Amy Chapman
Hello Amy,
Thank you for contacting us. We received all 3 of your emails: Livewello does not diagnose any health condition whatsoever, and certainly not Porphyria. Please visit our user-community contributed Gene Library to learn how it works-- Be sure to read the Disclaimers. Finally, we only provide Customer Support via the "Help" button at https://livewello.com/support Thank you
So 23andme.com & Livewello again for emphasis DOES NOT DIAGNOSE ANY OF THE PORPHYRIA DISEASE.
This is very important we ask that you read the information on Expert Porphyria testing below:
We are always most happy to help find you an expert or knowledable Dr to test, diagnose and treat for your specific type of Porphyria. Please contact us at 1-866-APF-3635
Diagnostic Testing for the Acute Porphyrias - Clarification of Testing Results
It has come to our attention that some patients who have been diagnosed clinically as having Acute Intermittent Porphyria (AIP) or another acute hepatic porphyria could not be confirmed by either biochemical or DNA testing. Biochemical testing is the demonstration of increased urinary ALA and PBG, and these values are highest during an acute attack when patients are symptomatic. Some patients can have high levels in between attacks as well, but not all. Positive diagnostic values should be increased greater than 5 times normal, not just a slight increase (less than 3 times normal) which can occur with dehydration. Most commercial laboratories and in particular the Porphyria Lab at the University of Texas Medical in Galveston which is run by Dr. Karl Anderson, will perform these tests properly. It is important that the doctor order urinary ALA and PBG and not a "porphyrin profile."
DNA, or molecular genetic testing, for the acute porphyrias is performed by sequencing the causative gene for the three major acute porphyrias and finding a specific pathogenic lesion on the gene, called a mutation. The technique used for DNA testing is at least 98% accurate, and patients with significantly elevated PBG are most often found to have a specific mutation. In our experience of testing over 1000 patients with or without elevated urinary PBG, only a few cases did not have a specific mutation. For these patients, we undertake special testing to look for gene deletions or other aberrations that would be responsible for a cryptic mutation.
During the last few years, our experience with DNA testing for the acute hepatic porphyrias has revealed certain mutations which are not pathogenic but are relatively frequent in normal individuals who do not have any acute hepatic porphyric symptoms. These are called polymorphisms and they are benign. When we recognize patients who have such polymorphisms, we continue to look further at their DNA to see if we can find a pathogenic mutation in addition. If no pathogenic mutation is found, we would have to classified or reclassify these patients as not affected. As you may be aware this has created great concern for patients who respond well to acute porphyria treatment that their treatment would be discontinued. We appreciate this concern and would like to have such patients physicians contact us so that we can discuss their situation, recommend additional testing to determine if their symptoms may have been misdiagnosed and institute appropriate treatment.
Diagnosing Acute Porphyria
The acute porphyrias include Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and d-Aminolevulinic Acid Dehydratase Porphyria (ADP). AIP is the most common of the acute porphyrias. The most common symptoms are acute attacks of severe abdominal pain, back pain, pain in the arms and legs, nausea, vomiting, rapid heartbeat and other symptoms. These attacks generally last for several days, and can be sporadic or happen frequently (~once/month). These acute attacks are very rare in children before puberty. These acute attacks are very rare in children before puberty. Attacks are often provoked by certain drugs, alcohol, hormones, infections, and perhaps stress. HCP and especially VP may cause blistering skin photosensitivity as well as acute attacks; AIP has no skin involvement, it is characterized just by these acute attacks.
A diagnosis of one of the acute porphyrias is made in two ways:
By biochemical testing:
For AIP- a urine porphobilinogen (PBG) test during an acute attackthe urine PBG level will be very high if the symptoms are caused by an acute porphyria (greater than 5 times the normal value)
For HCP and VP- a urine porphobilinogen (PBG) test during an acute attack if the patient has acute symptoms, or plasma porphyrins if the patient has skin symptoms
By genetic testing looking at the genes known to cause the acute porphyrias
There are many misconceptions about the urine PBG testing, its reliability, and urine color of patients with acute porphyria. The urine sample for PBG testing needs to be protected from light; the sample should be wrapped in tin foil or placed in a brown opaque bag after collection. However, if the sample is exposed to light for a little while (a few minutes) this will not affect the results. Please follow the directions provided by the laboratory when doing this testing.
Urine PBG testing can be sent to many labs including Quest, LabCorp, Mayo, ARUP, UTMB and Mount Sinai; they all do this testing reliably.
Many patients have urine that is red/purple in color when they have an acute attack, but this is not always the case. Patients can still have elevated urine PBG levels even if their urine color is normal. These misconceptions may lead to improper testing, or misdiagnoses. Physicians who suspect a patient has an acute porphyria should call one of the expert Porphyria centers in the US to consult (http://www.rarediseasesnetwork.org/porphyrias/index.htm).
The Difference between Active and Latent Acute Porphyria
It is important to know that ~80% of people who have changes in their porphyria genes (called mutations) never have symptoms of the acute porphyrias. These people are said to have latent acute porphyria.
If someone has a mutation in an acute porphyria gene and reports symptoms similar to an acute attack, their urine PBG level should be checked. If the urine PBG level is normal then there is likely another cause to this persons symptoms. Acute attacks are distinguished from other conditions that cause abdominal pain by very high PBG levels.
Treatment of Acute Porphyria
For patients with confirmed diagnoses, during acute attacks Panhematin infusions are administered as treatment and the pain is managed with various other medications. For more information on Panhematin please visit: http://www.aiporphyria.com/healthcare-professionals/treating-AIP/dosing
If someone who does not have a confirmed diagnosis of acute porphyria, documented by very high PBG levels, is having symptoms that seem consistent with an acute porphyria attack Panhematin is administered at the discretion of the treating physician. Generally all other causes of abdominal pain which are much more common than acute porphyria are ruled-out first. If Panhematin is administered and subsequently the diagnosis of acute porphyria cannot be confirmed by elevated urine PBG values or DNA testing, then it would be concluded that the attack is not caused by an acute porphyria. Even after Panhematin treatment, or after an acute attack has passed, the urine PBG levels should still be elevated for several days to a week. These levels may not be as high as they were during the acute attack, but will still be elevated.
Please note that we encourage you to consult with your Physician with any questions. If you are looking to get tested for Porphyria we have labs in the US that would be able to help you get a proper diagnosis. For the nearest Porphyria Lab please call 1-866-APF-3635 Part 2 Interview with 23andme Rep: Information from Porphyria Expert Dr Desnick:
DNA Diagnosis of Porphyria- Important Clarifications
by: Robert Desnick, M.D., PhD.
It has come to our attention that some Porphyria patients have sent their DNA to 23andMe or to other commercial companies, and have gotten results suggesting that they have DNA confirmed Porphyria. We are concerned that results from companies other than DNA testing laboratories that have experience in diagnosing porphyrias may provide patients with misleading information.
A major issue with DNA testing is whether a gene alteration (variant or mutation) is pathogenic (disease-causing) or benign (a change in the gene that does not cause or make one at-risk for the disease). For example, 23andMe does NOT do gene sequencing, but does determine if you have various gene alterations in the porphyria genes, all 57 of which are benign, and are not disease-causing but occur in a particular gene in which other lesions are in fact disease-causing. The benign lesions usually are identified by an #rs number. These benign changes are quite common but may lead a patient to believe that he/she has one or more porphyrias. They do not affect the heme biosynthetic enzymes, as they are not pathologic lesions. Of the gene lesions that cause disease, over 98% would be identified by gene sequencing as is done for all the Porphyrias at the Mount Sinai Laboratory and four Porphyrias at the Mayo Laboratory.
The Mount Sinai Genetic Testing Laboratory provides Porphyria DNA testing for all eight Porphyrias, and has a full-time Porphyria Genetic Counselor, Dana Doheny, MS, who is available to assist in arranging testing and interpreting the results. Typical time from receipt of sample to result is about two weeks. If the patient has biochemical-positive results and a DNA alteration cannot be found, there is a 1-2% chance that the patient has a cryptic mutation or a large deletion in the porphyria gene that is difficult to find by sequcning. The Mount Sinai Laboratory will do additional analyses to find the Porphyria gene lesion, if the patient has one.
Mayo Laboratories test for only three of the four Acute Porphyrias and for Erythropoietic Protoporphyria. To our knowledge they provide sequence results, and do not report polymorphisms..
Desiree notes: Dr Desnick is one of the most famous genetisists in the world. In fact, he is one of only three board certified in the US. See what he has to say about 23 and me. etc.
I emailed and did an interview with Claire @ 23andme
First question: Amy Apf, Oct 13, 9:15 AM:
Question can you diagnose diseases such as Porphyria Disease which is very rare and done by genetic testing only. I would like a response to this as this has caused much confusion. DNA and RNA testing for Porphyria research can only be done through a few places in the world. Do you have a solid explanation for this. Many people are sending their kits in to you saying yes they have this deadly disease but when tested properly with Labs such as blood, urine and feces through DNA they do not have it and thus have there diagnosis taken away or worse cant receive the needed medication because Porphyria disease is a registered Orphan Rare disease. PLEASE EXPLAIN
Thank you for contacting the 23andMe Team. No, 23andMe is not and has never been a diagnostic service.23andMe Services are for research, informational, and educational use only. We do not provide medical advice and the service has not been approved by the FDA for diagnostic testing.
Additionally, 23andMe does not provide health reports to customers who have purchased on or after November 22, 2013. Per an ongoing regulatory review with the FDA, new customers receive uninterpreted raw genetic data, as well as ancestry information.
Even when health information was available, porphyria was not a topic addressed by our health reports.
Please let us know if you have any additional questions.
Best Regards,
Clare
The 23andMe Team
Statement to Claire: I must say that thousands are flocking to your website for all sorts of disease both common and rare to receive all their medical input as you are the bible for diagnosing ppl. Do you know that this is happening and telling a few thousand people and others with a rare disease that for a few hundred bucks all there questions r solved they bring this info to there Drs and dr say sure you have it and if they were to get true genetic testing which is very expensive 4-8 k out of pocket no ins pays for this and must wait months 12 plus weeks for a true diagnoses. Then when they get 23 and me testing done they are entitled to costly medications and if diagnosed or implied a diagnose it could cost them their life. our medications r like chemo pricing hundreds of thousands of dollars an orphan drug approved by FDA I think there should be a big disclaimer and a clearer picture of what your services provide this is serious you don't even know. How do you fix this I would like the head person to email me his plans to help clarify your services and products what it does not due! Please explain my dilemma
Answer from Claire: We have had many other instances and we need an explanation or statement Please look at what an Expert Dr of Porphyria @ MT Sinani NY has said regarding testing and here is an example of what patients are telling people to do does this seem right to you. We would like Andew Page to respond or someone in Corporate this is outrageous.
DNA Diagnosis of Porphyria- Important Clarifications
by: Robert Desnick, M.D., PhD.
It has come to our attention that some Porphyria patients have sent their DNA to 23andMe or to other commercial companies, and have gotten results suggesting that they have DNA confirmed Porphyria. We are concerned that results from companies other than DNA testing laboratories that have experience in diagnosing porphyrias may provide patients with misleading information.
A major issue with DNA testing is whether a gene alteration (variant or mutation) is pathogenic (disease-causing) or benign (a change in the gene that does not cause or make one at-risk for the disease). For example, 23andMe does NOT do gene sequencing, but does determine if you have various gene alterations in the porphyria genes, all 57 of which are benign, and are not disease-causing but occur in a particular gene in which other lesions are in fact disease-causing. The benign lesions usually are identified by an #rs number. These benign changes are quite common but may lead a patient to believe that he/she has one or more porphyrias. They do not affect the heme biosynthetic enzymes, as they are not pathologic lesions. Of the gene lesions that cause disease, over 98% would be identified by gene sequencing as is done for all the Porphyrias at the Mount Sinai Laboratory and four Porphyrias at the Mayo Laboratory.
The Mount Sinai Genetic Testing Laboratory provides Porphyria DNA testing for all eight Porphyrias, and has a full-time Porphyria Genetic Counselor, Dana Doheny, MS, who is available to assist in arranging testing and interpreting the results. Typical time from receipt of sample to result is about two weeks. If the patient has biochemical-positive results and a DNA alteration cannot be found, there is a 1-2% chance that the patient has a cryptic mutation or a large deletion in the porphyria gene that is difficult to find by sequcning. The Mount Sinai Laboratory will do additional analyses to find the Porphyria gene lesion, if the patient has one.
Mayo Laboratories test for only three of the four Acute Porphyrias and for Erythropoietic Protoporphyria. To our knowledge they provide sequence results, and do not report polymorphisms..
Desiree notes: Dr Desnick is one of the most famous genetisists in the world. In fact, he is one of only three board certified in the US. See what he has to say about 23 and me. etc.
Please note a mutual client has suggested:
Member of Porphyria Statement: "Do yourself the biggest favor and bypass all labs and go directly online to 23andme.com and get your DNA done. then take the raw data to livewello.com to interpert the raw data into understandable reports. Best thing that I ever did. In 19__ the lab tests only showed that I had porphyria not what kind. The genetic test revealed that I have 2 kinds HCP and EPP. No percription needed, private and all for under 200.00"
APF: While anything is possible having one types of porphyria is vary rare in itself so to say two types a one that is acute and one that cuteanous. We have Porphyria centers around the world and encourage all persons to locate the nearest porphyria center in the country you live in to get genetic testing done. DNA testing does average 8 weeks or more but then you will have the answers from DNA testing. 1-866-APF-3635
Not only this is horrible advice to give from patient to patient but the fact that she said she was told to do this by your company or not this is true please clarify this is a rare orphan disease DNA is the way to diagnose the only way so anything your company can help us to distinguish would be so helpful not to tear away from sales profits or helping people but they must be a way to explain it better.
Amy Apf, Nov 9, 11:58 AM:
We have had many other instances and we need an explanation or statement Please look at what an Expert Dr of Porphyria @ MT Sinani NY has said regarding testing and here is an example of what patients are telling people to do does this seem right to you. We would like Andew Page to respond or someone in Corporate this is outrageous.
Clare, Nov 11, 11:31 AM:
Hi Amy,
Thank you for bringing this to our attention. The 23andMe Personal Genome Service should not be used as a substitute for a physician's advice. We take measures to make this clear to our customers.
The 23andMe Personal Genome Service has never had a health report on Porphyria. We do provide customers with access to their raw data, however, we note the statement at the top of our "Browse Raw Data" page has key limitations with regard to the data, including the following: "This data has undergone a general quality review however only a subset of markers have been individually validated for accuracy. As such, the data from 23andMe's Browse Raw Data feature is suitable only for research, educational, and informational use and not for medical or other use."
We also direct your attention to Section 5 of our Terms of Service: Risks and Considerations
Regarding 23andMeServices, which reads "The Genetic Information provided by 23andMe is for research, informational, and educational use onlyThe Services are not intended to be used by the customer for any diagnostic purpose and are not a substitute for professional medical advice. You should always seek the advice of your physician or other health care provider with any questions you may have regarding diagnosis, cure, treatment, mitigation, or prevention of any disease or other medical condition or impairment or the status of your health." The Terms of Service document is presented during registration and must be agreed to prior to customers receiving their reports or other personalized information through our service. A link to our Terms of Service also can be found at the bottom of each page on our website, and is provided here for your reference: https://www.23andme.com/about/tos/
Please let us know if you have any further questions.
Best regards,
The 23andMe Team
So according to Claire @ 23andme.com they DO NOT diagnosis Porphyria Disease. Thus they ask you to refer you to your Doctor, if your Dr needs care on how to test, diagnosis or treat a patient with any of the porphyria's the APF has a wonderful database of Doctors that can help. Please call for a free patient packet or have a Dr Kit sent to your Physician by calling 1-866-APF-3635 "Remember.Research is the key to your cure!"
"Remember.Research is the key to your cure!"
23and me. What is this all about? What can it do and what it Cannot do
Wednesday - November 11, 2015 @ 15:16:50
The 23andMe Difference.
Receive an overview of your DNA your 23 pairs of chromosomes
through detailed reports, tools and more.
What does this do for you? 1. Carrier Status reports If you are starting a family, find out if you are a carrier for an inherited condition. 2 .Ancestry reports Your DNA can tell you about your family history.3. Wellness reportsYour genetics can help you make more informed choices about your diet and exercise4. Traits reports Explore what makes you unique, from food preferences to physical features.
A new way to see yourself.
Genotyping is a great way to start understanding how your genetics can impact your life. It's a new filter. More knowledge to understand what makes you, you.
The world of genetics changes everyday and we are committed to keeping you informed and knowledgeable so you can continue your genetic journey throughout your life.
Being a "carrier" means you "carry" one genetic variant for a condition. Carriers do not typically have the genetic condition, but they can pass a genetic variant down to their children. If both parents are carriers, there is a 25% chance their child will have the condition.
Understanding your carrier status helps you work with your doctor to prepare for the health of your future family
**** NOT ABLE TO DIAGNOSE OR TELL YOU HAVE PORPHYRIA AND WHAT TYPE****
All carrier status reports
REPORT
GENE
VARIANTS
RELEVANT ETHNICITIES
ARSACS
SACS
1 Variant
French Canadian
Agenesis of the Corpus Callosum with Peripheral Neuropathy
SLC12A6
1 Variant
French Canadian
Autosomal Recessive Polycystic Kidney Disease
PKHD1
3 Variants
N/A
Beta Thalassemia and Related Hemoglobinopathies
HBB
10 Variants
Cypriot, Greek, Italian, Sardinian
Bloom Syndrome
BLM
1 Variant
Ashkenazi Jewish
Congenital Disorder of Glycosylation Type 1a (PMM2-CDG)
PMM2
2 Variants
Danish
Cystic Fibrosis
CFTR
28 Variants
European, Hispanic/Latino, Ashkenazi Jewish
D-Bifunctional Protein Deficiency
HSD17B4
2 Variants
N/A
Dihydrolipoamide Dehydrogenase Deficiency
DLD
1 Variant
Ashkenazi Jewish
Familial Dysautonomia
IKBKAP
1 Variant
Ashkenazi Jewish
Fanconi Anemia Group C
FANCC
3 Variants
Ashkenazi Jewish
GRACILE Syndrome
BCS1L
1 Variant
Finnish
Glycogen Storage Disease Type Ia
G6PC
1 Variant
Ashkenazi Jewish
Glycogen Storage Disease Type Ib
SLC37A4
2 Variants
N/A
Hereditary Fructose Intolerance
ALDOB
3 Variants
European
Leigh Syndrome, French Canadian Type
LRPPRC
1 Variant
French Canadian
Limb-Girdle Muscular Dystrophy Type 2D
SGCA
1 Variant
Finnish
Limb-Girdle Muscular Dystrophy Type 2E
SGCB
1 Variant
Southern Indiana Amish
Limb-Girdle Muscular Dystrophy Type 2I
FKRP
1 Variant
European
MCAD Deficiency
ACADM
3 Variants
Northern European
Maple Syrup Urine Disease Type 1B
BCKDHB
2 Variants
Ashkenazi Jewish
Neuronal Ceroid Lipofuscinosis (CLN5-Related)
CLN5
1 Variant
Finnish
Neuronal Ceroid Lipofuscinosis (PPT1-Related)
PPT1
3 Variants
Finnish
Niemann-Pick Disease Type A
SMPD1
3 Variants
Ashkenazi Jewish
Nijmegen Breakage Syndrome
NBN
1 Variant
Eastern European
Nonsyndromic Hearing Loss and Deafness, DFNB1 (GJB2-Related)
GJB2
2 Variants
Ashkenazi Jewish, European
Pendred Syndrome and DFNB4 Hearing Loss
SLC26A4
6 Variants
N/A
Primary Hyperoxaluria Type 2
GRHPR
1 Variant
European
Rhizomelic Chondrodysplasia Punctata Type 1
PEX7
1 Variant
N/A
Sickle Cell Anemia
HBB
1 Variant
African
Sjögren-Larsson Syndrome
ALDH3A2
1 Variant
Swedish
Tay-Sachs Disease
HEXA
4 Variants
Ashkenazi Jewish, Cajun
Tyrosinemia Type I
FAH
4 Variants
French Canadian, Finnish
Usher Syndrome Type 1F
PCDH15
1 Variant
Ashkenazi Jewish
Usher Syndrome Type 3A
CLRN1
1 Variant
Ashkenazi Jewish
Zellweger Syndrome Spectrum (PEX1-Related)
PEX1
1 Variant
N/A
Our tests can be used to determine carrier status in adults, but cannot determine if you have two copies of the genetic variants. The tests are not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On their own, carrier status tests are not intended to tell you anything about the health of your fetus, or your newborn childs risk of developing a particular disease later in life.
This is PART 1 In two days look for the interview from 23and me with APF
"Remember.Research is the key to your cure!"
The Genetic Science Learning Center
Monday - November 9, 2015 @ 15:01:12
The Genetic Science Learning Center
We invite you to check out the learning resources about the genetic science. The Genetic Science Learning Center at The University of Utah is a nationally and internationally-recognized education program that translates science and health for non-experts. In addition to genetics, we address all areas of life science and health as well as other scientific fields.
The GSLC's websites are one of the most used science sites on the Internet. In 2013, they received almost 20 million visits, which came from virtually every country in the world.
The American Porphyria Foundation promotes comprehensive care necessary for treating individuals with Porphyria. This section of our website offers suggestions for finding a local doctor who can manage your Porphyria, options for having your doctor consult a Porphyria specialist, and information on arranging a visit to a Porphyria clinic.
Because Porphyria is so rare, few physicians have experience treating patients with the disease. Most patients are in fact treated But the APF can help by putting your doctor's office in touch with a Porphyria specialist who can offer guidance on your care.
For those who need a diagnosis, you may be able to obtain a consultation at Porphyria clinic. Call the APF to reach a porphyria expert at a porphyria center. The APF office will also guide you to doctors who are not experts but are knowledgeable about porphyria. You may be asked to send your blood, urine, and stool samples for evaluation in advance of a clinic appointment. Especially if you plan to travel for a consultation, it is a good idea to call ahead and explain that you would like to be evaluated for Porphyria so that you can be sure you have done any necessary testing in advance. If local video conferencing facilities are available, telemedicine consultation with a Porphyria expert is also available.
Regardless of your situation, it is best to establish a good relationship with a doctor in your area. Developing a relationship with a primary care physician takes time and can be frustrating, particularly when you have difficulty finding a doctor who will manage your care. In this section of the website, you will also find Tips for the Doctor's Office that may help.
If you're having trouble finding a local doctor, the following organizations' doctor finder or physician referral services could be helpful. The APF does not recommend or endorse the doctors listed through these sites.
If you would like to read about supporting programs to ensure the quality of specialists in the field of porphyria, please see our Protect Our Future campaign information.
Tips for the doctor's office
Make Lists You may not always need to share all of your information with every doctor you see but the following items are particularly important: A list of all of your medications and needed refills, a summary of your medical history, a list of your recent tests, a list of your questions, concerns and new information, forms your doctor needs to address,
Plan Ahead For Your Doctor Visit Prepare your questions and a list of your symptoms, ( For example, racing heart, blisters, etc) Be concise. When you schedule your appointment, ask if you should have test results or other medical records sent to the doctors office before your visit. Nothing is worse than rescheduling for new tests you could have taken earlier or not had with you.
At Your Visit Be on time. Give and expect respect. Bring your lists and tell the doctor what you want to discuss and your goals for the visit. Be as brief as possible. Communication is an especially important skill. Make every word count because the doctor may only have 15 minutes to spend with you.
Be sure you understand what the doctor is advising you. If not, ask questions until you understand. If there is not enough time for all of your questions: Ask for handouts and brochures that will give you more information or schedule another visit.
You and your doctor may have different goals for the visit. For example, your doctor may want to just check your blood pressure, while you may have worries about possible surgery.
Many things can get in the way of helpful communication; emotions, communication style, different goals and lack of time all work against us. When emotions are high, logic is low. If you find that your emotions are interfering with your visit, explain this to your doctor. Try taking a moment to reflect on what you want to say and try again.
Lastly, you may feel that you know more about certain aspects of porphyria than your physician. Major medical journal articles are usually best accepted than internet articles.
After the Visit Often patients have questions they forgot to ask. If it is urgent, call the office right away. Otherwise, check the educational materials to see if the question can be answered there.
If you still dont have the answer, call your doctor. However, it is best to have the question clearly written. Be aware that the doctor may not be able to answer your call until the end of the day, but a nurse or physicians assistant may be able to help earlier.
"Remember.Research is the key to your cure!"
Research News
Monday - November 2, 2015 @ 15:08:30
Research News
We would like to let you know that the two satellite clinics in Seattle, WA and Miami, FL are now accepting Longitudinal Study patients for research. Another research center in Cleveland, OH will be ready to accept patients soon.
There are very important research studies ongoing right now that need research volunteers.
Everyone can participate in the Longitudinal Study. All you need to do is fill out questionnaires that reveal important facts about porphyria if enough people enter the study.
Volunteers are needed for the Natural History part of the Alnylam Study to show the potential of their drug to prevent attacks. Fly down and back to the research centers with all expenses paid for you.
Research volunteers are also needed for the Panhematin study to verify that Panhematin can be used to prevent attacks. Although patients have been given the drug for a long time to prevent attacks, this study will give doctors the better evidence.
It is important to join the registry (http://www.rarediseasesnetwork.org/porphyrias/index.htm), so that your name will go directly to the researchers. If you need help with the registry, just call the APF and Natalia or Jessica will help you.For details on how you can participate, call the APF at713.266.9617.
"Remember.Research is the key to your cure!"
Please Join, Get Involved, Volunteer for Research: Join the Registry
Friday - October 30, 2015 @ 12:26:54
Please Join, Get Involved, Volunteer for Research:
Join the Porphyria Registry and LET THE GOVERNMENT KNOW THEY MUST PROVIDE FUNDING FOR PORPHYRIA RESEARCH!!!!!
To join the Contact Registry, click here to open a page that lists all of the rare disease consortia. Scroll down the page until you come to the Porphyria Consortium and click on your type of porphyria. You will then be asked to complete a simple form including information about the date of your diagnosis, if you know it. If you have copies of your initial diagnostic lab results, you may want to have them handy when you go to the registry website.
Porphyria experts have created this National Porphyria Registrya type of partnership between doctors and patients as a way for those with porphyria to share information about their health and treatment so physicians can learn from their experience and use that knowledge to enhance diagnosis, treatment and eventually find a cure for porphyria.
It is the best means to prove that there are enough porphyria patients who want improved health care. If we don't speak up, we will be left behind when research funding is given. We DO NOT HAVE ENOUGH PEOPLE ON THE REGISTRY. Please join the registry.
Joining the Porphyria Registry is anonymous and free of charge. All data will be stored in a secure, computerized database. No personal identifying information (such as your name, address, telephone number) will be given to anyone without your expressed approval.
_________________________________________________
The registry is not linked to APF membership, but we hope you will join the American Porphyria Foundation too! So please consider joining the Contact Registry, and thank you for continuing to be a member of the APF.
Doctors who study rare diseases see a relatively small number of sufferers over many years of practice. This Registry will give a big boost to medical and scientific understanding of porphyria by bringing together information from patients all over the country.
If you need help enrolling in the registry contact our office toll free at 1-866-APF-3635.
"Remember.Research is the key to your cure!"
DON'T FORGET TO FALL BACK THIS WEEKEND!
Thursday - October 29, 2015 @ 17:51:28
Please don't forget to fall back this weekend!
DNA Diagnosis of Porphyria- Important Clarifications by: Robert Desnick, M.D., PhD
Monday - October 26, 2015 @ 10:30:02
DNA Diagnosis of Porphyria- Important Clarifications
by: Robert Desnick, M.D., PhD.
It has come to our attention that some Porphyria patients have sent their DNA to 23andMe or to other commercial companies, and have gotten results suggesting that they have DNA confirmed Porphyria. We are concerned that results from companies other than DNA testing laboratories that have experience in diagnosing porphyrias may provide patients with misleading information.
A major issue with DNA testing is whether a gene alteration (variant or mutation) is pathogenic (disease-causing) or benign (a change in the gene that does not cause or make one at-risk for the disease). For example, 23andMe does NOT do gene sequencing, but does determine if you have various gene alterations in the porphyria genes, all 57 of which are benign, and are not disease-causing but occur in a particular gene in which other lesions are in fact disease-causing. The benign lesions usually are identified by an #rs number. These benign changes are quite common but may lead a patient to believe that he/she has one or more porphyrias. They do not affect the heme biosynthetic enzymes, as they are not pathologic lesions. Of the gene lesions that cause disease, over 98% would be identified by gene sequencing as is done for all the Porphyrias at the Mount Sinai Laboratory and four Porphyrias at the Mayo Laboratory.
The Mount Sinai Genetic Testing Laboratory provides Porphyria DNA testing for all eight Porphyrias, and has a full-time Porphyria Genetic Counselor, Dana Doheny, MS, who is available to assist in arranging testing and interpreting the results. Typical time from receipt of sample to result is about two weeks. If the patient has biochemical-positive results and a DNA alteration cannot be found, there is a 1-2% chance that the patient has a cryptic mutation or a large deletion in the porphyria gene that is difficult to find by sequcning. The Mount Sinai Laboratory will do additional analyses to find the Porphyria gene lesion, if the patient has one.
Mayo Laboratories test for only three of the four Acute Porphyrias and for Erythropoietic Protoporphyria. To our knowledge they provide sequence results, and do not report polymorphisms..
Desiree notes: Dr Desnick is one of the most famous genetisists in the world. In fact, he is one of only three board certified in the US. See what he has to say about 23 and me. etc.
A Microbiologist Recreated 'Starry Night' With Bacteria In A Petri Dish And it's not too shabby.
Thursday - October 22, 2015 @ 18:10:00
AGAR ARTby Melanie Sullivan of Missouri
If only Vincent van Gogh could have lived to see this strikingly accurate reproduction of his iconic "Starry Night" -- especially since, instead of oil on canvas, the work is a bacteria on petri. Because even with these most minute of materials, the night sky still swirls with a palpable momentum of wind, fog and moonlight.
The work of science-savvy art is the product of Melanie Sullivan, a microbiologist who submitted her microscopic masterpiece to the American Society for Microbiology's first Agar Art contest. The competition invited microbiologists to get in touch with their cultural sides in more ways than one, exploring the infectious beauty of infectious bacteria.
The multitalented scientists used proteins, yeast and good ol' fashioned bacteria to create visions of flowers, skeletons, butterflies -- even a map of New York City. Check out all of thestunning submissions here, and see the winning works below.
A Microbiologist Recreated 'Starry Night' With Bacteria In A Petri Dish
And it's not too shabby.
If only Vincent van Gogh could have lived to see this strikingly accurate reproduction of his iconic "Starry Night" -- especially since, instead of oil on canvas, the work is a bacteria on petri. Because even with these most minute of materials, the night sky still swirls with a palpable momentum of wind, fog and moonlight.
The work of science-savvy art is the product of Melanie Sullivan, a microbiologist who submitted her microscopic masterpiece to the American Society for Microbiology's first Agar Art contest. The competition invited microbiologists to get in touch with their cultural sides in more ways than one, exploring the infectious beauty of infectious bacteria.
The multitalented scientists used proteins, yeast and good ol' fashioned bacteria to create visions of flowers, skeletons, butterflies -- even a map of New York City. Check out all of thestunning submissions here, and see the winning works below.
Posted: 10/20/2015 09:38 AM EDTEdited: 4 hours ago
AGAR ARTby Melanie Sullivan of Missouri
If only Vincent van Gogh could have lived to see this strikingly accurate reproduction of his iconic "Starry Night" -- especially since, instead of oil on canvas, the work is a bacteria on petri. Because even with these most minute of materials, the night sky still swirls with a palpable momentum of wind, fog and moonlight.
The work of science-savvy art is the product of Melanie Sullivan, a microbiologist who submitted her microscopic masterpiece to the American Society for Microbiology's first Agar Art contest. The competition invited microbiologists to get in touch with their cultural sides in more ways than one, exploring the infectious beauty of infectious bacteria.
The multitalented scientists used proteins, yeast and good ol' fashioned bacteria to create visions of flowers, skeletons, butterflies -- even a map of New York City. Check out all of thestunning submissions here, and see the winning works below.
A Poem of Encouragement
Tuesday - October 20, 2015 @ 18:06:28
Frequently asked questions about Porphyria!
Wednesday - October 14, 2015 @ 13:40:48
Frequently Asked Questions
General Questions:
How does one get porphyria? Most porphyrias are inherited. However, one type, Porphyria Cutanea Tarda (PCT), may either be inherited (also referred to as familial) or sporadic due to various environmental factors. In each type of porphyria there is a deficiency of a specific enzyme. These enzymes are involved in the synthesis of heme, a substance important to many body functions and are found in large amounts in bone marrow and red blood cells (which contain hemoglobin), and also has an important function in the liver and muscles. The type of porphyria present is determined by which enzyme is deficient; these enzyme deficiencies are usually inherited. Environmental factors, such as drugs, chemicals, diet, and sun exposure can, depending on the type of porphyria, greatly influence the severity of symptoms.
How are the porphyrias inherited? Can my children inherit porphyria from me? The inherited porphyrias are either autosomal dominant (inherited from one parent), autosomal recessive (inherited from both parents), or X-linked (the gene is located on the X-chromosome). Autosomal genes always occur in pairs, with one inherited from each parent. Individuals with an autosomal dominant form of porphyria have one non-working gene paired with a working (or normal) gene. Each of their children has a 50% chance of inheriting the non-working gene. Some of those who inherit the non-working gene will develop symptoms. Individuals with an autosomal recessive type of porphyria have a pair of non-working genes, and each of their children will inherit one non-working gene for that porphyria which will be paired with the working gene of their partner. Such individuals are referred to as carriers and will not have any symptoms. If two carriers of the same autosomal recessive porphyria have children, each child will have a 25% of inheriting a non-working gene from each carrier parent, and having the disorder. Because all porphyrias are uncommon, it is very unlikely that more than one type of porphyria will occur in the same family, or that a person with one type of porphyria will go on to develop another type. However, patients with more than one type of porphyria have been reported.
How are the porphyrias classified? The best way to classify a case of porphyria is to determine which enzyme is deficient, or not functioning properly. Normally these enzymes act in a sequence to make heme from simpler molecules. Heme is a vital substance for all body organs and consists of an iron atom surrounded by a porphyrin molecule. If a specific enzyme is not made properly or there is not enough of the enzyme, it cannot function properly and that step in the heme-making process cannot proceed.
Sometimes other classifications are useful. Most commonly the porphyrias are divided into the acute and cutaneous porphyrias, depending on the primary symptoms. The acute porphyrias [Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and ALA-dehydratase Deficiency Porphyria (ALD)] present with sudden attacks of severe stomach pain that last for several days; VP and HCP may also have skin symptoms. The cutaneous porphyrias present with blistering and scarring of the skin, pain, and/or redness and swelling in sun-exposed areas. The porphyrias may also be classified as hepatic or erythropoietic, depending on the organ where the porphyrins accumulate, the liver for the hepatic porphyrias [AIP, HCP, VP, Porphyria Cutanea Tarda (PCT), and Hepatoerythropoietic Porphyria (HEP)] or the bone marrow for the erythropoietic porphyrias [Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EPP), and X-Linked Protoporphyria (XLP)].
What treatment and prevention are available? To date, there is no cure for any of the porphyrias. Treatment and prevention depends on the type of porphyria. Preventive measures, which include avoidance of certain drugs and alcohol, as in the hepatic porphyrias, and sun exposure, as in the erythropoietic porphyrias, are also important in those individuals who are identified as having inherited porphyria, even if they have never had symptoms. For the acute porphyrias, hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required with monitoring of salt and water balance. Harmful drugs should be stopped. Attacks are treated with either glucose loading or intravenous administration of hemin (Panhematin). Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices.
PCT, both familial and sporadic, can be treated with regularly scheduled phlebotomies (removal of blood) to lower the amount of in the liver or a low dose regimen of hydroxychloroquine as well as removal of factors (for example, certain medications) that activated the disease.
Treatment of the cutaneous porphyrias is dependant on the specific porphyria. For CEP, blood transfusions to correct anemia, splenectomy (removal of the spleen) are often needed treatments. Bone marrow transplant (BMT) has also been done in severe cases with good results. For EPP, treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance. Avoidance of sunlight (and fluorescent lights for CEP) is recommended for all individuals with a cutaneous porphyria as well as those diagnosed with HCP or VP who have porphyria-related sun sensitivity.
Is porphyria progressive or lethal? Unlike some genetic disorders in which all individuals who inherit a gene mutation become ill,the severity of porphyria varies considerably. Such variability is due to certain additional factors other than the gene itself. Consequently, risks of severe medical difficulties or even death in the acute porphyrias are often diminished when affected individuals are well informed of their diagnosis and adopt suggested precautionary measures. Even with modern treatment and prevention, some patients still have repeated attacks. However, progressive deterioration and death from paralysis in the acute porphyrias are very unusual.
Should doctors be informed that an individual has porphyria, even if it is latent? Yes! The diagnosis of porphyria is always an important item of medical information, even when there are no symptoms. It may, for example, influence the choice of drugs to treat other conditions, the choice of anesthesia for surgery, or dietary recommendations.
What diagnostic tests are available? There are many laboratory tests available for the porphyrias, and it is often difficult to decide which should be chosen. Many of these tests are expensive. The results are often difficult to interpret. The tests vary in sensitivity and specificity. If a test is sensitive, it is unlikely to be falsely negative (that is, fail to diagnose porphyria in a patient who has the disorder). If a test is specific, it is unlikely to be falsely positive (that is, diagnose porphyria in a patient who does not have the disorder). Certain tests are both sensitive and specific in patients who have symptoms that are suggestive of a porphyria. It is advisable to have the testing performed by a laboratory that has expertise in the clinical aspects of porphyria and can provide a valid interpretation of the test results. If testing has been performed in laboratories other than porphyria laboratories, consultation with a porphyria expert is advised before a final diagnosis is made.
When abdominal and neurological symptoms suggest an acute porphyria, the best screening tests are urinary aminolevulinic acid (ALA) and porphobilinogen (PBG). When there are cutaneous symptoms that suggest porphyria, the best screening test is a plasma porphyrin assay. If one of these screening tests is abnormal, more extensive testing, including urinary, fecal, and red blood cell porphyrins, are often indicated. Urinary, fecal, and red blood cell porphyrin measurements are not very useful for initial screening because they lack either sensitivity or specificity and, therefore, are often difficult to interpret. Measurement of heme biosynthetic enzymes in red blood cells or lymphocytes is not appropriate for screening unless it is part of a family study that is done after someone in the family is already known to have a specific enzyme deficiency.
DNA testing to identify the specific mutation in an individuals porphyria-causing gene may be indicated to confirm the diagnosis of a specific porphyria. Before requesting DNA testing, it is recommended that patients have biochemical testing (urinary, stool and/or plasma porphyrins and porphyrin precursors (ALA and PBG) and/or enzyme assays). However, many patients have not had an acute attack or are not symptomatic at present, so biochemical testing may be inconclusive.
In contrast, DNA testing is the most accurate and reliable method for determining if a person has a specific porphyria and is considered the "gold standard" for the diagnosis of genetic disorders. If a mutation (or change) in the DNA sequence is found in a specific Porphyria-causing gene, the diagnosis of that Porphyria is confirmed. DNA analysis will detect more than 97% of known disease-causing mutations. DNA testing can be performed whether the patient is symptomatic or not. Once a mutation has been identified, DNA analysis can then be performed on other family members to determine if they have inherited that Porphyria, thus allowing identification of individuals who can be counseled about appropriate management in order to avoid or minimize disease complications.
What is latent porphyria? If my doctor told me that I have latent porphyria, does this mean that I will never have any symptoms? Individuals with a disease-causing mutation without symptoms have "latent" porphyria. However, this does not mean that such an individual will never have symptoms. Genetic factors (that is, the presence of a porphyria-causing gene mutation is not the only factor involved. Exposure to certain environmental factors, such as drugs, chemicals, diet, and sun exposure can, depending on the type of porphyria, greatly influence whether an individual with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms. There may also be additional factors, including additional genes, that may modify the symptoms. This is why it is important that all family members of individuals diagnosed with porphyria be tested whether they have symptoms or not, and that all individuals who have a confirmed diagnosis of porphyria be educated about and follow the recommended precautionary and preventive measures for porphyria.
Where can I find a porphyria expert? What other type of doctor can diagnose me properly and what type of specialist should I see if I have porphyria. There are several Porphyria experts in the US and outside the US, including the Porphyria Centers in this Consortium. Information about other experts can be obtained by contacting the American Porphyria Foundation (www.porphyriafoundation.com) or one of the Porphyrias Consortium members. If a porphyria is suspected, any physician can order the appropriate tests. Since interpretation of these results may be difficult, it is best for the physician or healthcare professional to consult with a porphyria expert for an accurate interpretation of the results and, if necessary, advice about additional testing, treatment, or prevention and precautionary measures.
Can I have more than one type of porphyria? Because all porphyrias are uncommon, it is very unlikely that more than one type of porphyria will occur in the same family, or that a person with one type of porphyria will go on to develop another type. However, patients with more than one type of porphyria have been reported.
Can porphyria improve with age? The symptoms of porphyria do not improve with age, per se. Untreated, the symptoms and the secondary effects of long-term symptoms will get worsen over time. However, with proper diagnosis, treatment of acute attacks (in the acute porphyrias), and following recommended preventive measures, it is possible that symptoms may be lessened.
Should I be tested often? How often? Monitoring of porphyrin levels and other follow-up testing is dependent on the type of porphyria and the medical status of the individual. It is, therefore, important that a person who has been diagnosed with porphyria be followed by a porphyria expert.
Does porphyria affect my liver? Should I have liver tests? Liver function tests should be performed routinely on all individuals diagnosed with porphyria.
Do people have liver transplants for poprhyria? Liver transplantation may be beneficial for individuals with end-stage liver disease as a result of porphyria.
My doctor diagnosed me with porphyria but the porphyria expert said I did not have it. Why would this happen and should I be retested? Such a situation needs to be dealt with on an individual basis. Whether further testing is recommended depends on how the patient was initially diagnosed and how the porphyria expert made the decision that porphyria is not the diagnosis. The results of biochemical testing are sometimes interpreted incorrectly by a physician who is not an expert in porphyria. Review of the results of the biochemical testing by a porphyria expert may determine that the results are not consistent with what is typically seen in a patient with porphyria during an attack. The results of DNA analysis may also contribute to the porphyria expert saying that it is unlikely that the patient has porphyria. DNA analysis, although considered to be the gold standard for diagnosis, is not perfect in that the patient may have a mutation in a part of the porphyria gene that is not analyzed by routine testing or the patient has a mutation in a porphyria gene that was not analyzed. In the event that a diagnosis of porphyria is still suspect, then it is recommended that the patient undergo additional biochemical testing at the time of an acute attack. Additionally, further testing may include DNA analysis for other acute porphyrias (if only one or two were tested).
Is porphyria research being conducted? How can I volunteer to participate in research?
Yes. For additional information about research being conducted and how to volunteer to participate, please contact either the Porphyrias Consortium Coordinator by email (porphyria.center@mssm.edu) or telephone (212-659-6779) or one of the site coordinators (see list of Porphyrias Consortium Members for locations and contact information).
Acute Porphyrias
Does surgery or pregnancy pose additional risks? Porphyria-related risks of surgery and pregnancy depends on the type of porphyria. Surgery may increase the risk of an attack of the acute porphyrias. This risk can be greatly reduced if certain precautions are taken, including the type of anesthesia used. The patients surgeon and anesthesiologist should consult a porphyria expert prior to hospitalization for surgery. Such consultation may also be helpful during pregnancy. Although attacks of acute porphyria can occur during pregnancy, the risk appears to be less than formally thought. Treatment of acute attacks during pregnancy is feasible.
What drugs are safe and unsafe? For information about safe and unsafe drugs in the acute porphyrias, it is best to consult the American Porphyria Foundation Acute Porphyrias Drug Safety Database (http://www.porphyriafoundation.com/drug-database) or the European Porphyria Initiative (http://www.porphyria-europe.org/03-drugs). The databases contain expert assessments of the potential of drugs to provoke attacks of acute porphyria (AIP, VP, HCP & ADP) based on the available evidence. However this evidence is not always complete, which may lead to some degree of uncertainty. The information in these databases is meant as guidance to health care professionals. It must be made clear that the prescription of drugs to a patient with acute porphyria is entirely at the risk of the physician in charge.
Since most commonly used drugs have not been tested, they should be avoided if at all possible. If a question regarding drug safety arises, a physician or medical center specializing in porphyria should be contacted.
Can men have acute porphyria? Yes. Since the acute porphyrias are inherited in an autosomal dominant pattern, males and females are equally at risk for having an acute porphyria. Exposure to certain environmental factors, such as drugs, chemicals, and diet, greatly influence whether an individualmales and females--with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms. However, one of the environmental is hormones, and, therefore, attacks are more common in women than in men. Women may experience cyclical acute attacks associated with their menstrual cycle, starting in puberty. Such attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high.
Do I need a special diet with porphyria? Nutritional recommendations for the acute porphyrias emphasize a high carbohydrate intake as part of a balanced diet that provides all essential nutrients. The recommendations include an adequate intake of dietary fiber, vitamins and minerals. The goals are to prevent acute attacks of Porphyria that may be related to diet, avoid deficiencies of nutrients, and maintain a normal body weight. More information on diet on theAmerican Porphyria website (http://www.porphyriafoundation.com)
Will porphyria affect my thinking and memory? Generally, the acute porphyrias do not affect thinking and memory. However, a person may experience some neurological effects, including confusion, convulsions, muscle weakness, and, rarely, paralysis, due to effects on the nervous system.
What precipitates a porphyria attack? In an individual with an acute porphyria, an acute attack can be brought on by certain drugs, hormones in women, environmental factors including chemicals of various types, nutrition including fasting and low carbohydrate diets, alcoholic beverages, medical and physical stress, and physical fatigue.
I have acute porphyria: Can I do the following: take a flu shot, donate my organs, take aCAT scan with the contrast? Flu shots are not contraindicated for individuals diagnosed with acute porphyria, and can be taken safely. Any immunizations appear to be okay. In fact, since other illnesses can bring on a porphyria attack, remaining healthy is one of the most important ways to prevent acute attacks.
There has been no information to date to suggest that CAT scans with or without contrast agents should not be performed on an individual with porphyria.
Organ donation would be up to a particular transplant program or network. In acute porphyrias any organ should be acceptable except perhaps the liver. In the case of PCT organ donation would most likely be acceptable in the absence of a history of hepatitis C or HIV.
What should I do if the drug I need is on the unsafe list? Drugs on the unsafe list are those drugs that should be avoided by individuals diagnosed with an acute porphyria because they have been found to provoke an acute attack in some individuals. If a drug prescribed for an individual diagnosed with an acute porphyria is on the unsafe list, the prescribing physician should check the Drug Database for a safe alternative. No drug should be withheld if it is judged essential for optimum treatment of a life-threatening condition (e.g. chemotherapy for cancer). The risk versus the benefit should be assessed and discussed with the patient. For help with this assessment you may wish to contact a Porphyria expert. It may be recommended that a patient undergo biochemical monitoring in the early stages of treatment It must also be noted that response to drugs in patients with an acute porphyria is extremely variable and individuals may be encountered who have used an unsafe drug without adverse effect.
Cutaneous Porphyrias
Is sunlight always harmful? Sun sensitivity can occur in all but two types of porphyria, specifically AIP and ADP. The degree of sensitivity to sunlight varies considerably. Patients with sun sensitivity have high levels of porphyrins in the blood plasma which, depending on the type of porphyria, have originated from the liver or the bone marrow. Ultraviolet light interacts with porphyrins in such a way as to damage skin tissue. Some treatments may help patients tolerate sun exposure even without lowering porphyrin levels. In some cases, treatment can lower porphyrin levels and sunlight can be tolerated.
Should I use a special sunscreen? Most patients with a cutaneous type of porphyria must learn to avoid sunlight as much as possible. Protective clothing may also be recommended. For patients with EPP, treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance but does not lower porphyrin levels. Over-the-counter sunscreens and over-the-counter beta carotene (vitamin A) is not effective.
The APF will be exhibiting at the 57th American Hematology Society meeting in Orlando , Fl. The convention is held from December 5 to 8. We would like to ask you to help us man the exhibit booth.
We hand out physician education materials at the convention for the 8000 attendees. Since many of you visit with hematologists, and since hematologists treat and diagnose many patients, we attend the ASH meeting each year as a part of our physician education program.
As the premier event in malignant and non-malignant hematology, this meeting will provide attendees with an invaluable educational experience and the opportunity to:
Review more than 3,000 scientific abstracts highlighting the updates in the hottest topics in hematology
Interact with the global community of more than 20,000 hematology professionals from every sub-specialty
Attend the hallmark Education and Scientific Program sessions
Network with top minds in the field
Please volunteer to help man the booth. For details, contact us at 866.APF.3635.
"Remember.Research is the key to your cure!"
Genetics 101 of Porphyria
Thursday - October 8, 2015 @ 10:30:02
Genetics 101: Basic genetics and inheritance
In order to better understand the Porphyrias and how the disorders are inherited, it is helpful to understand some concepts of basic genetics and inheritance patterns.
DNA, Chromosomes, and Genes:
Deoxyribonucleic acid (DNA) is a nucleic acid that contains the instructions used in the development and functioning of all known living organisms and some viruses. DNA is often compared to a set of blueprints or a recipe or a code because it contains the instructions needed to make certain proteins, which are the complex molecules that do most of the work in our bodies. Each of these proteins has a specific function in the cell, and, ultimately in how the organism develops, its physical makeup, and how it functions day-to-day. The DNA segments that carry this genetic information are called genes. The size of each gene varies greatly, and there are about 20,000 genes that are distributed along the 23 pairs of chromosomes.
A DNA molecule is a twisted double-strand of building blocks, called nucleotides. It is like a twisted ladder, with the vertical stringers made of phosphates and sugars and the rungs made of pairs of nucleotides. There are four nucleotides in DNA: adenine (A), thymine (T), guanine (G), and cytosine (C). Also important is that on each rung of this ladder, A always pairs with T, and G always pairs with C. These nucleotides along the ladder are like letters in a word, and put together in their specific order make up the words in a detailed set of instructions. These instructions are read using a special code, called the genetic code.
Within cells, DNA is organized into long structures called chromosomes. A chromosome is like a cookbook with many recipes (or genes) that tell the body how to function. The human body is made up of trillions of cells and over 200 different cell types like various blood, liver, and brain cell types. Each cell contains 46 chromosomes. Each chromosome can be identified by its relative size and location of the centromere, a constriction in the chromosome.
The chromosomes come in pairs. Since there are 46 chromosomes, there are 23 pairs of chromosomes. One chromosome in each pair comes from the persons father. The other chromosome in each pair comes from the mother.
The first 22 pairs of chromosomes are called autosomes. The autosomes are numbered 1-22. These chromosomes determine an indivduals physical appearance and tell the body how to function day-to-day.
The 23rd pair of chromosomes is called the sex chromosomes. Parts of these chromosomes determine whether an individual will be male or female, but they also carry additional important information. A female has two X chromosomes. A male has one X chromosome and one Y chromosome.
Along each chromosome, there are thousands of genes. Since the chromosomes come in pairs, the genes along them also come in pairs. This means that the genes that are found on one chromosome in each pair are the same as the genes that are found on the other chromosome in that pair. The sex chromosomes are an exception. Most of the genes that are located on the X chromosome are different from the genes that are located on the Y chromosome. For example, the ALAS2 gene, involved in X-linked Erythropoietic Protoporphyria (EPP), is on the X chromosome, but is NOT on the Y chromosome.
Each gene is a set of instructions that tells the cell how to make a specific product called a protein. These proteins have the job of telling the body how to grow and develop as well as how to do all the things that are necessary for the body to work properly every day. Any change in one of these genes may interfere with the bodys ability to make one of these necessary proteins. A gene change is called a mutation.
Autosomal Dominant Inheritance:
Since autosomal genes always occur in pairs, with one coming from each parent, individuals with an autosomal dominant form of porphyria [Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), familial Porphyria Cutanea Tarda (f-PCT)] have one non-working gene with a mutation on one chromosome, paired with a working (or normal) gene on the other chromosome. Usually, the non-working gene was inherited from one of the individuals parents. Rarely, a new mutation (also called a de novo mutation) can occur in the affected individual and not be present in one of his parents. However, the de novo mutation will be inherited by 50% of the patients offspring. In individuals with an autosomal dominant form of porphyria, there is a 50% chance with each pregnancy that the non-working gene will be passed on to a child. Some of those who inherit the non-working gene will develop symptoms.
Autosomal Recessive Inheritance:
Individuals with an autosomal recessive type of porphyria [Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EEP) and Hepatoerythropoietic Porphyria (HEP)] have a pair of genes with mutations that affects the function of the enzyme encoded by the gene. In such individuals, one mutant gene was passed on from each of their parents. If their children only inherit one mutant gene for that porphyria, which will be paired with a normal gene from the other parent, and the child will be a carrier, but will not have symptoms.
If two carriers of the same or similar mutant recessive gene have children, there is a 25% chance with each pregnancy that the child will inherit two mutant genes (one from each carrier parent), and these children will develop symptoms of the disease.
X-Linked Inheritance:
The sex chromosomes are the X-chromosome and the Y-chromosome. Females have two X-chromosomes, and males have one X-chromosome and one Y-chromosome. In X-linked disorders [for example, X-Linked Protoporphyria (XLP], the gene is located on the X-chromosome, and the risk for children depends on the gender of the affected parent. If a female has the mutation, there is a 50% risk for passing the mutation onto her children with each pregnancy.
X-linked inheritance (when the mother has the mutation)
If a daughter gets the gene mutation from either her mother or her father, the daughter may or may not have symptoms, and the severity of symptoms may vary even among the females in the same family. For this reason, in most X-linked disorders, including X-Linked Protoporphyria, females who have the gene mutation are referred to as heterozygous for the mutation, rather than carriers which infers that they will not have any symptoms (as in autosomal recessive disorders). If a son gets the mothers mutation, he will have symptoms.
Clinuvel and FDA discuss EPP indication and regulatory pathways for SCENESSE
Wednesday - October 7, 2015 @ 13:07:55
Clinuvel and FDA discuss EPP indication and regulatory pathways for SCENESSE
The attached document discusses the latest news from FDA and Clinuvel:
Type C meeting provides guidance for follow up and further discussions between FDA and Clinuvel.
Clinuvel Pharmaceuticals Limited (ASX: CUV; ADR:CLVLY; XETRA:DAX) today announced that on September 30 it met in Silver Spring, USA, with the US Food and Drug Administration's (FDA's) Division for Dermatology and Dental Products (DDDP) and representatives of the Center of Drug Evaluation and Research (CDER). The objective of the meeting was to discuss the US regulatory review of SCENESSE (afamelanotide 16mg) to be made available to American erythropoietic protoporphyria (EPP) patients. In 2014 SCENESSE was granted marketing authorisation by the European Medicines Agency as a prophylactic photoprotective drug for adult EPP patients.
The DDDP stated that it was seeking a regulatory pathway to make SCENESSE available in the US, and the regulatory avenue of Accelerated Approval was suggested, pending FDA's review, analyses and further discussions on available photoprovocation and data on quality of life in EPP patients.
A discussion was held on the drug's benefits to patients who had received SCENESSE. Expert European and US porphyria clinicians were invited to share their experience in the treatment of EPP patients and the use of SCENESSE in their patients. Further discussions will be held with the DDDP following the review of photoprovocation and quality of life data.
"Remember.Research is the key to your cure!"
CME Course share with your Medical community today
Monday - October 5, 2015 @ 10:30:01
New Continuing Medical Education Course CME
Exciting New Continuing Medical Education CourseCME With Drs Herbert Bonkovsky, Lisa Kehrberg and Brendan McGuire.
Medscape has produced an outstanding new physician education video that can be found on the Medscape website.
Acute Intermittent Porphyria: A View From the Trenches:
Herbert Bonkovsky, MD; Brendan M. McGuire, MD, MS; Lisa Kehrberg, MD CME/CE Released: 09/25/2014; Valid for credit through 09/25/2015
Please advise your physicians of this free CME course for CME credit. You, too, can watch the video by joining the complimentary Medscape online site. http://www.medscape.org/viewarticle/831382.
You can register easily and view this and other porphyria videos, as well as a host of additional excellent articles written about all types of porphyria.
Our thanks to Dr Bonkovsky, Dr Kehrberg and Dr McGuire.
AIP Research Experiences
Friday - October 2, 2015 @ 10:30:07
Will you help with medical research?
Why is important?
What does it entail?
When does this research happen?
What Happens?
Take a look at a few who have expressed why research is so important!
Tracy Yelen ~ Research Experience
Type of Porphyria:
Acute Intermittent Porphyria (AIP)
"If you're at all interested in what they are doing to me in this Panhematin trial, I am happy to share. During the entire stay, the medical team accessed my port. They drew all the blood they wanted without all the usual IV sticks, which is nice. Every morning after breakfast we did the infusions, which may or may not be a placebo. Neither the nurses nor I were allowed to see what was pumping into me. So I am blindfolded and there are sheets hung in the room to cover the medicine and tinfoil around the lines. It takes only a couple hours to complete. I snoozed and chatted with the sweet nurse. Outside of that, the dextrose fluids are flowing in through my port 24/7. Otherwise, it was pretty uneventful. Why do I tell you this? Basically, I want to remind you of how important it is to volunteer as a research patient if you ever get the opportunity. There are lots of trials that even perfectly well people can do for various different studies and various different medical reasons."
~Tracy Yelen, AIP
Steve Stevens ~ Research Experience
Type of Porphyria:
Acute Intermittent Porphyria (AIP)
"I volunteered for the Alnylam Study about a month ago and yesterday (March 30) I went to Birmingham, Alabama to do the initial Observation Part of it. The APF set up everything to get me there and back home. Jessica handled all the travel arrangements and I can't say enough of the awesome job she did. I didn't have any layovers longer than 45 minutes. That was amazing because I have had layovers in the past last for hours. Thank You Jessica for the great itinerary and asking for any input before you booked the flight. Before I forget, the plane tickets, food, taxi costs, etc. was covered by the APF. It didn't cost me a penny. I got to meet Dr. Bloomer and Dr. Singal. They explained to me what the Study was and answered all my questions. I haven't met many doctors like them, after talking to them I could see and feel their sincerity about helping us. They are great. The Study Administrator's name is Toni and she is so fantastic. She sat with me and explained the paperwork in detail and answered any questions I had pertaining to the Study or questionnaires that I was answering. I was very impressed how professional and organized she is. She made sure everything was completed and I had enough time to get back to the airport in time for my trip home. She and the doctors are very special people. I cannot say enough about them.
I am glad I volunteered for the Study and would encourage anyone that has one of the acute porphyria's to do so also. I hope to volunteer for future research and hope others do too. You are helping yourself, your family and your future generations."
~ Steve Stevens, AIP
"Remember.Research is the key to your cure!"
Your APF Membership
Wednesday - September 30, 2015 @ 10:30:06
Your APF Membership
We are currently working on the next issue of the Newsletter, where you can find latest news, updates and stories from the porphyria world.Our members, who made deductible charitable contributions, will receive the fresh issue.
The APF is able to maintain our physician and patient education programs and many other services because of your support. Since we do not receive government funding, we need your support and donations. Is your membership and contact information up to date? If you have moved, please update us with your current address. Be sure to send us your email address so you can receive the E-news.
Support the APF with AmazonSmile for Charitable Organizations!
You can also support the APF through the AmazonSmile program! Amazon will donate 0.5-0.8% of the price of your eligible purchases to us, at no cost to you. Please make us your choice of a charitable organization, support the research while shopping!
Please note, the program will only be available to shoppers who visit Amazon via a special web address - smile.amazon.com - instead of the normal Amazon.com homepage.
It is easy and free, AmazonSmile is the same Amazon you know. Same products, same prices, same service. Thank you for supporting us!
According to Porphyria experts, approximately 80% of individuals who carry a gene mutation for acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria, and remain asymptomatic, and others may have only one or a few acute attacks throughout life. In most of these cases levels of ALA, porphobilinogen, and porphyrins in urine, serum, and feces are normal. Additionally, most patients with ALA-dehydratase deficiency porphyria also remain asymptomatic for most of their lives. Severe abdominal pain, the most frequent symptom, is diffuse rather than localized and is often accompanied by nausea, vomiting, bloating, constipation, and sometimes diarrhea. Other symptoms include insomnia (often an early symptom), heart palpitations, seizures (sometimes due to salt imbalance in the body as a result of excessive vomiting and/or diarrhea), restlessness, hallucinations, and other acute psychiatric symptoms.
The common symptoms of the acute porphyrias include:
Abdominal pain: severe, diffuse, usually lasting for hours or longer
Vomiting
Constipation
Diarrhea
Pain in extremities, back, chest, neck, or head
Loss or impairment of movement
Respiratory paralysis
Behavioral changes, including agitation, confusion, hallucinations, and depression.
Convulsions, as a result of excessive vomiting and/or diarrhea
Increased heart rate
The Cutaneous Porphyrias
The most common symptoms of the cutaneous porphyrias are photosensitivity and/or skin fragility. Photosensitivity presents within minutes of exposure to sun and some types of artificial light with severe burning pain especially on the back of the hands, the face, and the top of the feet. Attacks may last for 23 days, and are usually unresponsive to any pain medication except cold air and cold water. Except in EPP, this is often accompanied by painful blisters which can take weeks to heal, may bleed, and result in scarring and changes in skin color at the sites of the blisters. In CEP, this photosensitivity may lead to mutilation and loss of facial features and fingers. Patients with PCT, HEP, and CEP may also present with increased hair growth, typically on the temples. Additionally in CEP, brownish-colored teeth which fluoresce under ultraviolet light and mild or severe hemolytic anemia are common.
The common symptoms of the cutaneous porphyrias include:
Sensitivity to sunlight
Fragile skin
Depending on the type of cutaneous porphyria, the following symptoms may also be present:
Blistering
Scarring
Changes in skin color
Increased hair growth
Anemia
Teeth discoloration
Bone fragility or bone loss, due to Vitamin D deficiency
"Remember.Research is the key to your cure!"
Experiences in Research Studies A Must read!
Friday - September 25, 2015 @ 12:05:02
Dear APF Members, family and friends:
I thought you would want to know that the APF has been collecting Research experience stories that are now on the APF Member stories section on the website labeled Research Experience (Next to their name)
Please take some time to read each members experience. We still need you to participate in research, we are rare so please take a few moments to consider volunteering your time for a wonderful cause. Feel free to click on the link above. Be a Medical Hero today!
Have a happy and healthy Autumn everyone! American Porphyria Foundation "Remember.Research is the key to your cure!"
Clinical Trials for Acute Porphyrias we still need you!
Wednesday - September 23, 2015 @ 10:30:09
We still need Medical Heroes for Acute Porphyrias. Part 2 Check out this one. Please contact the APF: 1-866-APF-3635 ask for Jessica or Natalia for more Information
A service of the U.S. National Institutes of Health
The purpose of this study is to evaluate the safety and tolerability of ALN-AS1 in AIP patients as well as to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of ALN-AS1 in AIP patients.
Drug: ALN-AS1 Drug: Sterile Normal Saline (0.9% NaCl)
Phase 1
Study Type:
Interventional
Study Design:
Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:
A Phase 1, Single-ascending Dose, Multiple-ascending Dose, and Multi-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN AS1 in Patients With Acute Intermittent Porphyria (AIP)
Further study details as provided by Alnylam Pharmaceuticals:
Primary Outcome Measures:
The safety of ALN-AS1 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation [ Time Frame: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 126 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
Profile of Pharmacokinetics (PK) of ALN-AS1 [ Time Frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 126 days post-dose ] [ Designated as safety issue: No ]
Cmax, tmax, AUC, t1/2
The change in delta-aminolevulinic acid (ALA) from baseline [ Time Frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 126 days post-dose ] [ Designated as safety issue: No ]
The change in Porphobilinogen (PBG) from baseline [ Time Frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 126 days post-dose ] [ Designated as safety issue: No ]
Estimated Enrollment:
48
Study Start Date:
May 2015
Estimated Study Completion Date:
July 2016
Estimated Primary Completion Date:
May 2016 (Final data collection date for primary outcome measure)
Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
History of multiple drug allergies or intolerance to subcutaneous injection
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02452372
Here is some New Information. Part 1 of 2 Press Release for the Acute Type Porphyrias
Monday - September 21, 2015 @ 18:14:47
Here is some New Information. Part 1 of 2 Press Release for the Acute Type Porphyrias
September 16, 2015
Dear Alnylam Patient Connect Community,
We are excited to share news of clinical progress with ALN-AS1, a subcutaneously administered (i.e., injection), investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias. On September 15th, we presented initial clinical data from our ongoing Phase 1 study of ALN-AS1 during an oral presentation at the International Congress of Porphyrins and Porphyrias (ICPP) in Dusseldorf, Germany.
You can read our press release and view our data presentation here.
We are very excited by the data from our ALN-AS1 program. On behalf of all of us at Alnylam, we are committed to advancing this novel, investigational medicine for people living with hepatic porphyrias.
Sincerely, Alnylam Patient Connect
Note: If you are a patient, we encourage you to speak to your physician to obtain information about our clinical trials. Detailed information about our trials can be found atclinicaltrials.gov.
SCENESSE Released for European Distribution
Monday - September 21, 2015 @ 10:30:01
SCENESSE Released for European Distribution
Clinuvel Pharmaceuticals Limited (ASX: CUV; ADR:CLVLY; XETRA:DAX) announces today that the European Medicines Agencys (EMAs) Pharmacovigilance and Risk Committee (PRAC) has agreed to a Post Authorisation Safety Study (PASS) protocol, allowing SCENESSE (afamelanotide 16mg) to be released for the commercial supply to adult patients diagnosed with erythropoietic protoporphyria (EPP). While SCENESSE was granted European marketing authorisation by the European Commission on 22 December 2014, it has taken a further nine months to gain agreement on the proposed PASS protocol.
Today we would like to tell you about the upcoming undertaking from the Cook family. As you may know, the Cook brothers, Cason and Caul, have EPP and have set a great example about enhancing awareness of the disease in their local area. They have been hosting a Hat Day for many years in their home town of Vernon, TX. This year, in addition to a Hat Day, Cason & Caul are hosting The Shadow Race (benefit barrel race) in Vernon, TX in November. They are getting some t-shirts together to sell as well. We appreciate all your support in raising awareness!
Be it orange, be it green, perhaps red, or maybe black
In the end though only purple is on our mind
They don't have that purple here
here, it's nowhere to be found
Embrace that you are special
a rare precious gem
We are Porphyria strong!
"Remember.Research is the key to your cure!"
ALC
Porphyria: A Lyon's Share of Trouble an Update
Monday - September 14, 2015 @ 10:00:03
If you read the first edition, you will want to read what has happened over the past ten years.
In this remarkable updated book, Desiree offers an information rich discussion of the porphyrias, a group of rare metabolic diseases. She also discusses her own case, as well as those of many other patients whom she has helped over the past thirty five years as co-founder and Executive Director of the American Porphyria Foundation.
Desiree embraces the challenges of porphyria with courage and humor and writes about them in an open and honest dialogue. After twenty-five years as a medical writer, she has delineated the new and exciting developments in the treatments of all the porphyrias, offering explanations about this complicated group of diseases in a readable manner.
Every patient and family member will derive tremendous insight and guidance from Desirees experience, as well as vital information to aid in navigating the complexities involved in confronting and surmounting the porphyrias.
*All proceeds from Porphyria: A Lyon's Share of Trouble an Update go directly to the American Porphyria Foundation. http://www.amazon.com/dp/B014WZX26M ~ To order your copy today
"Remember.Research is the key to your cure!"
We need you! Longitudinal Study of the Porphyrias
Monday - September 7, 2015 @ 10:30:00
Longitudinal Study of the Porphyrias
We are looking for patients volunteers for the 7201 Longitudinal Study of the Porphyrias. The purpose of this long-term follow-up study is to provide a better understanding of the natural history of porphyrias, as affected by available therapies, and to aid in developing new forms of treatment. You will be working closely with porphyria experts and researchers.
Volunteering for research is the most important action you can take to change your future health because Research is the Key to Your Cure. You can be a Medical Hero and join many patients, who gave some of their time to help find important answers leading to new and improved treatments and a cure.
To find out more information and participate in a study, please contact us at the APF 866-apf-3635 to be put in touch with the study center closest to you.
"Remember.Research is the key to your cure!"
PCT- Facts from NIH
Friday - September 4, 2015 @ 14:27:06
Phlebotomy, known also as bloodletting or venesection, is a major therapeutic procedure that has been performed by physicians in various civilisations since antiquity up to the present1,2. In the past it was practised using cupping, lancets or by the application of leeches2. This procedure often weakened the patient and resulted in his or her death. A famous example is that of President George Washington who died in 1799 following the removal of approximately 1.7 litres of blood during a bloodletting procedure for acute epiglottitis3. Originally, several thousand years ago, phlebotomy was used for the treatment of various disorders, but in addition to its therapeutic benefits, phlebotomy also had a preventive role. In present day medicine, phlebotomy can be performed in physicians offices, at a blood bank or in hospital under the supervision of a doctor after obtaining a medical prescription stating the indication and number of phlebotomy sessions required. Currently, therapeutic phlebotomy is approved for three main indications: haemochromatosis, polycythaemia vera and porphyria cutanea tarda. It has also been used as a treatment alternative for many other diseases in various countries, especially in Chinese medicine, although these indications are not approved by western medicine.
Porphyria cutanea tarda
Porphyria cutanea tarda (PCT) is a rare metabolic disorder caused by uroporphyrinogen decarboxylase deficiency that leads to the accumulation of uroporphyrinogen and highly carboxylated porphyrins in the liver, plasma, urine and sometimes faeces. There are three types of PCT: two familial and one sporadic. Most of the cases are sporadic (80% approximately) and have been associated with several risk factors such as alcohol abuse, hepatitis C, oestrogen use, smoking, hepatic siderosis and human immunodeficiency virus infection55. Hepatitis C is one of the most important risk factors; in a recent systematic review and meta-analysis, 50% of PCT patients were found to have hepatitis C infection suggesting an important role in the pathogenesis of PCT although the pathophysiology is still unclear56,57. HFE gene mutations, especially C282Y homozygosis, has also been found in PCT patients, which explains the iron excess in this disorder, although true haemochromatosis is rare57.
Clinically, PCT is characterised by chronic blistering skin manifestations that include photosensitivity, increased skin fragility with bullae, erosions, and hyper- or hypo-pigmentation that affects sun-exposed areas of the body; however, these skin manifestations are not specific and they do not confirm the diagnosis. Liver involvement is also common especially in the sporadic form with cirrhosis, fibrosis and increased risk of hepatocellular carcinoma54. The diagnosis of PCT requires both clinical and biochemical features. Laboratory investigations include porphyrin chromatographic separation that shows markedly increased uroporphyrins and heptacarboxyl porphyrins in plasma and/or urine, with lesser amounts of penta- and hexa-carboxyl porphyrins. Faecal porphyrins, consisting mainly of isocoproporphyrins, are also increased while the erythrocyte porphyrins are normal57. UROD activity analysis with gene sequencing is essential in familial PCT58.
Liver biopsy is indicated in the event of liver damage demonstrated by markedly increased serum transaminase levels, while skin biopsy is of little benefit because it often only shows sub-epidermal bullae with minimal inflammation54. An important aspect of treatment is the avoidance of any risk factors such as alcohol, excessive iron or oestrogen and hepatitis C that can potentially exacerbate the disorder. Therapeutic phlebotomy has long been considered the treatment of choice in most patients with PCT; hydroxychloroquine is the alternative treatment if phlebotomies cannot be tolerated59. According to Rocchiet al., 450 mL of whole blood should be removed during each phlebotomy session, with sessions repeated every 2 weeks until the haemoglobin level is below 11 g/ dL or until the serum ferritin level is below 20 ng/ mL, which is close to the lower limit of normal. Most patients require 6 months to achieve remission but clinical improvement may be noted during the third month after starting phlebotomy60. Hydroxychloroquine was found to be superior to phlebotomy in decreasing porphyrin production; however, liver disease was more severe in the hydroxychloroquine group61. No difference was seen between therapeutic phlebotomy and desferrioxamine injection62.
Skin blistering was the first sign to disappear in patients, at an average of 2 to 3 months and a maximum of 9 months; this was followed by improvement of skin fragility, hypertrichosis and hyper- or hypo-pigmentation while pseudoscleroderma may improve in some patients59. Urinary porphyrin levels return to normal but although liver function tests may improve following phlebotomy, the extent of liver damage does not improve63,64. Phlebotomy must be stopped after achieving remission or when iron deficiency anaemia occurs; however, relapse may occur during the first 5 years of treatment especially when risk factors are still present, such as excessive alcohol consumption65.
For the full article please use this link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934278/
"Remember. Research is the key to your cure!"
Dateline NBC documentary "Out of the Shadows" links
Wednesday - September 2, 2015 @ 10:30:02
Dateline NBC documentary "Out of the Shadows" links
If you missed a Dateline NBC documentary "Out of the Shadows", about children who must avoid sunlight because of their medical conditions, you can view it online on the NBC News website:
Friday Night Race Raises Awareness, Funds For Skin Disease
Around 200 people walked or ran in a 5-K fundraiser coordinated by owners of Triad Chick-fil-A.
Growing up in Alabama, Shawn Willis lived with a rare and obscure disease that, at least for himself and his parents, didn't have a name.
"I remember purple-like balloons sitting on top of my feet," he said." My head became so swollen, I couldn't hold it up."
Finally, when he was eight years old, a doctor finally gave a name to the disease that had made the boy so sensitive to light that he couldn't be in the sun without devastating damage.
It's called Porphyria, and it afflicts only about one in 250,000 people. According to the Mayo Clinic, it is a "group of disorders that result from a buildup of natural chemicals that produce porphyrin in your body. Porphyrins are essential for the function of hemoglobin."
There is no treatment, although Willis said one is now on the horizon, and no cure.
Willis and others want to change that.
On Friday evening, up to 200 people walked or ran in a five-kilometer fundraiser that was coordinated by owners of Triad Chick-fil-A. Willis owns the restaurant on University Drive, the site of the run/walk.
Organizers hoped to raise at least $7,000 for the American Porphyria Foundation.
Willis cannot stay in the sun without a wide-brimmed hat, sunglasses, gloves, long sleeve shirts and pants. He has to wear a mask when he's out in the
Growing up was hard, he said - "Imagine going to school as a sixth-grader wearing a sombrero and garden gloves" - but now, he keeps a keen sense of humor.
Otherwise, he said, he would become a recluse like so many who have the diseases.
He gets strange looks when he wears a mask, he said, particularly when he is at the airport or anywhere where security is a concern.
"There are people who who become bitter and live like hermits," he said. "They don't leave the house because of the way people treat you. But you can say, 'You know what? I'd rather be out here and made fun of rather than not to be out here."
Tristan Sterling of Timberlake volunteered at the event with his mother, Jennifer Spencer and brother, James Burnette.
"This really helps raise awareness," he said.
"Remember.Research is the key to your cure!"
Shayne Henkelmans story with AIP
Wednesday - August 26, 2015 @ 10:30:00
Shayne Henkelman
Type of Porphyria:
Acute Intermittent Porphyria (AIP)
My name is Shayne Henkelman from Calgary, Alberta, Canada and this is the story of how I came to be diagnosed with Acute Intermittent Porphyria.
Looking back now I displayed signs of the disease early on in my life. I had fairly chronic issues with my stomach and bowels up until the time I was about 7 years old. The doctors never really determined the cause from what I can recall and likened my issues to laziness and immaturity.
From the time I was 7 until I was 22 I lived a pretty normal symptom free life. In March of 1995 I was working on a service rig in the oil patch of Northern Alberta when I fell victim to an industrial accident which ended up with me having third degree full thickness burns to my right leg from the knee down. It was during the recovery process I started having unexplained attacks of severe abdominal pain and debilitating vomiting that would leave me crippled on the ground and always required trips to the Emergency Room to correct.
At first the popular consensus among the medical professionals was that my body was basically going through withdrawal from the very large amounts of opioid analgesics that I had been receiving for upwards of eight months to deal with the pain of the burn. That theory was soon to be disproven however as the length of time increased that I had been off the medication. The frequency and severity of the attacks also greatly increased to the point I was having an attack every 7 to 10 days, and presenting to whatever Emergency Room was closest every time.
Thankfully after about 3 years of this the attacks had seemed to decrease greatly, happening maybe only 3 or 4 times a year. During this time the doctors ran me through every test they could possibly think of to try and determine what was going on. Most of them showed nothing at all physically wrong, the only real consistent thing revealed was a greatly increased white cell count during every attack. The amount of theory, conjecture and false diagnosis during this time was ridiculous. Unresolved infection in the burn, crohns disease, colitis, irritable bowel, psychological disorder, and the ever present assumption of drug seeking. Between the stresses the attacks had on my body, and the associated feeling of being a lab rat for a system that was never going to figure out what was wrong with me I was in a very poor state of mind.
In 2001 I had a pretty severe attack that had the ER physicians and Internalists concerned enough that they decided to conduct an exploratory procedure to see if they could determine anything from an inside viewpoint. When I awoke I was informed that my gall bladder was rotten like a bad apple and that it had been removed. They assured me that it had been the sole issue of all my worldly woes and that in short order I should be feeling as good as new. I still remember the feeling of relief and elation when they said that to me. I also still remember the feeling of hopelessness I had 6 weeks later when I had my next attack.
Enter the second round of conjecture and theory, the whole while subjecting me to every test imaginable, numerous times, no matter how invasive. And I did them all, because I knew there had to be something wrong. The other alternative, that I was crazy, I just didnt want to accept.
In 2005 things took some interesting turns. Although my attacks still came every month or so I was feeling pretty good in May of that year. My sister and I decided to spontaneously drive down to Las Vegas for the weekend for a bit of fun. Oh what fun it was to beâ?¦ We stopped just outside of Vegas to eat, and as I took the first bite I knew an attack was imminent and sure enough it came on very fast and furious. I spent the first day laying in the hotel room while my sister went to the strip, with the exception of the 6 hours I was forced to lay outside in the blazing sun after having locked myself out of the room and not being able to get a new key as my sister hadnt registered my name on the room. Those with Porphyria can imagine the effect that had on my attack. When my sister came back I was in bad shape and she rushed me to the hospital.
They actually got me feeling better very quickly surprisingly. Or maybe it was my stubbornness of not wanting to miss the fun of Vegas, either way I signed myself out after about 20 hours against recommendations, leaving at about 8 in the morning. I enjoyed the most of the day, having a few minor issues but nothing serious. That changed come about 7 that evening when the attack started again, this time more severe than any other I had ever experienced. The first hospital refused to see me as I had signed myself out earlier. By the time we arrived at the next closest hospital I was literally near death. My liver had almost completely stopped functioning and I wound up in the ICU, and later admitted for two weeks before I was stable enough to take a flight back home.
The amount of pain that followed the next months was incredibly unbearable. My then GP worked through almost every painkiller there was with me before we found one that didnt have severe side effects of one sort or another, OxyContin, and I began taking it like crazy to control the pain.
In November of that year I finally had an appointment with a well-regarded GI specialist in Calgary. After telling him my symptoms and history he immediately said it sounded like a very rare disease that he had never actually encountered in his practice, Porphyria. After departing his office and doing my own research I had absolutely no doubt that finally I had the answer to my issues! Again I was ecstatic! The doctor ordered blood tests and the 24 hour urinalysis. And lo and behold, they both came back negative and the prognosis was dismissed by the doctor yet again.
After what I had read by professionals and other patients online I wasnt so quick to be dismissive however. After all, this was the only disease I had found where every symptom fit like a perfectly placed puzzle piece. I found out about the DNA testing that was available at Mt. Sinai and inquired about it. My GP was willing to set it up for me, the only drawback was it would cost $1000.00 US and not a penny of that was covered by either Government healthcare or my private insurance. I didnt let that stop me however. That month my landlord did not receive her rentâ?¦
Six weeks later the results were in and it was conclusive that I indeed did have AIP. I finally had an answer, and again I was ecstatic thinking that was the end of it! Unfortunately I was very, very wrong. You see, during this whole period my pain was still there, and due to my body becoming used to the pain medication the amount I was being prescribed kept going up and up. Eventually I was taking 80 mg of OxyContin every 4 hours, with maybe 4 or so Percocet in between doses for breakthrough pain. At one point I ran out of pain meds for a single day and felt horrible.
I bluntly asked my GP if I was becoming addicted and he assured me that OxyContin was not addictive according to the manufacturer Purdue Pharmaceuticals, and further Shayne, you have never struck me as having an addictive personality. So I continued with taking them as ordered. For years.
I really discovered how wrong he and Purdue were three months later when I arrived at his office for a scheduled appointment to find it locked and empty. 12 hours without the Oxy and I was at the hospital going through withdrawal. They refused to give me anything and the doctor flat out told me that my GP had caused a major epidemic of addiction in our small town with his very liberal prescribing of opioids. He told me that I should call the College of Physicians and Surgeons to inquire, which I did to find out his ability to prescribe medications had been suspended hence his quick closure.
I searched high and low to find a doctor to prescribe me more pain meds as I was getting very ill, all to no avail. Its hard to get a prescription for OxyContin when you are taking three times as much daily as the average terminal cancer patient. It came to a point I had to check myself into our Government funded detox center, which unfortunately is really nothing more than a place where you can lay in a corner and detoxify and they will call an ambulance if you happen to die. That was the worst 10 days of my life coming off that horrible medication, Im very thankful I did not have an attack during that time as Im sure I would not survived it.
However, I came out the other side as they say. And when I did, I threw every medication the doctor had me on away, and something very interesting happened. My attacks started to decrease. Instead of once every 4 to 6 weeks it became once every 8 to 10. Then once every 3 months or so, and then in December of 2010 I stopped having them at all.
In fact, I felt great. Better than I had in 15 years, it seemed as if the disease had gone into full remission. Could Porphyria do that? None of the few doctors I remained seeing had any idea, and frankly I didnt care because I was basking in the glory of my newfound health!
In 2012 I started a new career, in what was really a dream job for me. I was living a rock star like life, doing an incredible amount of traveling and interacting with a lot of very famous people. I was on top of the world. That is until 2013 when a trip to Montreal found me in the first attack I had been subject to since 2010. And then I had another. And another. And the cycle of attacks returned. The doctors at one point said that the shunt where I had my Gall Bladder removed had become infected and that it wasnt the disease flaring back up again. Again that proved to be just wishful thinking as the attacks continued, but mostly only when away on work trips.
In the first few months of this year I had three consecutive attacks on three consecutive trips that wound up with me being hospitalized. I really didnt have a choice but to stop doing the travel portion of my job, which has been a very hard pill to swallow in this ongoing battle with this horrible disease, but really I had no option as it almost seemed that it was the flying that was causing the attacks. My coworkers and I have exhausted ourselves thinking of possibilities of what is causing the attacks to happen, and every lead has proven unjustified in the end.
And now here I am. 20 years later and I really have no more answers than I did on the day of that first attack, besides having a name for what my condition is. I did have an incredible stroke of luck however as I was forced to have to replace my GP as I had not done that since my previous drug pusher vanished into the night. After trying a few I stumbled onto one where we really clicked. He took my case and has been the best doctor Ive ever encountered, very willing to work with me to find possible causes, and to ensure that my medication needs are accurate and monitored. In turn he has also referred me to an amazing GI specialist who has taken my case very seriously as well despite knowing nothing about Porphyria on the day I walked in to see him. He now has standing orders set up in my local ER to ensure I am treated properly while in attack, and is also fighting through the regulatory red tape to get me Heme treatments here in Canada.
I would love to be able to say Ive kept my chin up throughout this entire ordeal, but that would be an outright lie. Ive gone through a lot of very dark depressive episodes during these past years, Im sure that is a very common bond with every sufferer of Porphyria. In truth this is one of those diseases that I would never wish upon anyone, no matter how much I may dislike them.
And thats my AIP story in all its gritty glory and longwinded detail. There are points Im not proud of, the permanent opioid addiction that I have while still requiring the use of them for pain. The times Ive thought that it would be easier to end it all. I honestly thought about omitting those facts in this story, but then reconsidered as Im sure that a few or more fellow patients reading this will probably be able to relate to those issues.
If I could offer one piece of advice to any fellow Porphyria patient it would be to surround yourself with people that truly care about you. I am very lucky in the fact that since the recurrence I have a very strong support network in the coworkers I have mentioned previously. They are truly my rock, and its vitally important to have those sorts of people to help you through the low periods that are bound to occur whether you want them to or not.
I leave you with this quote by Maya Angelou;
I can be changed by what happens to me. But I will not be reduced by it.
~ Shayne Henkelman, AIP
"Remember.Research is the key to your cure!"
Dont Forgot To MOO'VE it
Tuesday - August 25, 2015 @ 10:30:00
The "MOVE IT IN THE MOONLIGHT RUN" In Burlington, NC on August 28, 2015
The location of the run is now determined: Chick-fil-A University Commons at 1477 University Dr. Burlington, NC 27215
Please register and join the awareness run. It was organized at night so that people with photosensitive porphyrias can participate too.
You can find out more details and information about the run on the website:
Bent Rods Bass Club Fundraising & The Barrel Race in Vernon, TX
Monday - August 24, 2015 @ 10:30:02
Bent Rods Bass Club Fundraising
We invite you to the Bent Rods Bass Club for the fundraising tournament. Bent Rods Bass Club strongly believes in giving back and in the Karma of helping others, so each year they pick a new Charity to support. For 2015 they have picked the APF. For fundraising event they will be hosting the Bent "mini" Rods Challenge and raffling off a custom built bait casting rod & reel.
We also would like to remind you about the upcoming undertaking from the Cook family. As you may know, the Cook brothers, Cason and Caul, have EPP and have set a great example about enhancing awareness of the disease in their local area. They have been hosting a Hat Day for many years in their home town of Vernon, TX. This year, in addition to a Hat Day, Cason & Caul are hosting The Shadow Race (benefit barrel race) in Vernon, TX in November. They are getting some t-shirts together to sell as well. We appreciate all your support in raising awareness!
"Remember..Research is the key to your cure!"
From NIH- A must Read
Friday - August 21, 2015 @ 10:30:02
From NIH A Must READ
Porphyria
Porphyrias are a group of rare disorders passed down through families. An important part ofhemoglobin, called heme, is not made properly. Heme is also found in myoglobin, a protein found in certain muscles.
Causes
Normally, the body makes heme in a multi-step process. Porphyrins are made during several steps of this process. Patients with porphyria are lacking certain enzymes needed for this process. This causes abnormal amounts of porphyrins or related chemicals to build up in the body.
There are many different forms of porphyria. The most common type is porphyria cutanea tarda (PCT).
Drugs, infection, alcohol, and hormones such as estrogen may trigger attacks of certain types of porphyria.
Symptoms
Porphyrias involve three major symptoms:
Abdominal pain or cramping (only in some forms of the disease)
Sensitivity to light that can cause rashes, blistering, and scarring of the skin (photodermatitis)
Problems with the nervous system and muscles (seizures, mental disturbances, nerve damage)
Attacks can occur suddenly. They often start with severe abdominal pain followed by vomiting and constipation. Being out in the sun can cause pain, sensations of heat, blistering, and skin redness and swelling. Blisters heal slowly, often with scarring or skin color changes. The scarring may be disfiguring. Urine may turn red or brown after an attack.
Other symptoms may include:
Muscle pain
Muscle weakness or paralysis
Numbness or tingling
Pain in the arms or legs
Pain in the back
Personality changes
Attacks can sometimes be life threatening, producing:
Low blood pressure
Severe electrolyte imbalances
Shock
Exams and Tests
Your doctor will perform a physical exam, which includes listening to your heart. You may have a fast heart rate (tachycardia). The doctor may find that your deep tendon reflexes (knee jerks or others) do not work properly.
Blood and urine tests may reveal kidney problems or other problems. Special tests can measure porphyrins in the blood.
Fluids and glucose to boost carbohydrate levels, which helps limit the production of porphyrins
Removal of blood (phlebotomy)
Depending on the type of porphyria you have, your doctor may tell you to:
Avoid all alcohol
Avoid drugs that may trigger an attack
Avoid injuring the skin
Avoid sunlight as much as possible and use sunscreen when outside
Eat a high-carbohydrate diet
Outlook (Prognosis)
Porphyrias are life-long diseases with symptoms that come and go. Some forms of the disease cause more symptoms than others. Getting proper treatment and staying away from triggers can help lengthen the time between attacks.
Respiratory failure (due to weakness of chest muscles)
Scarring of the skin
When to Contact a Medical Professional
Get medical help as soon as you have signs of an acute attack. Talk to your doctor about your risk for this condition if you have a long history of undiagnosed abdominal pain, muscle and nerve problems, and sensitivity to sunlight.
Prevention
Genetic counseling may benefit people who want to have children and who have a family history of any type of porphyria.
Anderson K. The porphyrias. In: Goldman L, Schafer AI, eds.Goldman's Cecil Medicine
Fuller SJ, Wiley JS. Heme biosynthesis and its disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, eds.Hematology: Basic Principles and Practice
Flash back from the New England Journal 1960 read and share
Tuesday - August 18, 2015 @ 14:45:14
*The second annual Chester M. Jones Lecture, presented in part at the Massachusetts General Hospital, Boston, March 18, 1960.
From the Department of Medicine, University of Minnesota Medical School and Hospitals.
Aided by the John and Mary Briggs Fund for Porphyria Research, and under a contract with the Research and Development Command, Surgeon General's Office, United States Army.
This was provided by the New England Journal good to read and keep
Genetics 101: Basic genetics and inheritance of Porphyria
Tuesday - August 18, 2015 @ 10:30:00
Genetics 101: Basic genetics and inheritance
In order to better understand the Porphyrias and how the disorders are inherited, it is helpful to understand some concepts of basic genetics and inheritance patterns.
DNA, Chromosomes, and Genes:
Deoxyribonucleic acid (DNA) is a nucleic acid that contains the instructions used in the development and functioning of all known living organisms and some viruses. DNA is often compared to a set of blueprints or a recipe or a code because it contains the instructions needed to make certain proteins, which are the complex molecules that do most of the work in our bodies. Each of these proteins has a specific function in the cell, and, ultimately in how the organism develops, its physical makeup, and how it functions day-to-day. The DNA segments that carry this genetic information are called genes. The size of each gene varies greatly, and there are about 20,000 genes that are distributed along the 23 pairs of chromosomes.
A DNA molecule is a twisted double-strand of building blocks, called nucleotides. It is like a twisted ladder, with the vertical stringers made of phosphates and sugars and the rungs made of pairs of nucleotides. There are four nucleotides in DNA: adenine (A), thymine (T), guanine (G), and cytosine (C). Also important is that on each rung of this ladder, A always pairs with T, and G always pairs with C. These nucleotides along the ladder are like letters in a word, and put together in their specific order make up the words in a detailed set of instructions. These instructions are read using a special code, called the genetic code.
Within cells, DNA is organized into long structures called chromosomes. A chromosome is like a cookbook with many recipes (or genes) that tell the body how to function. The human body is made up of trillions of cells and over 200 different cell types like various blood, liver, and brain cell types. Each cell contains 46 chromosomes. Each chromosome can be identified by its relative size and location of the centromere, a constriction in the chromosome.
Hello dear members, we have an open letter from Dr. Peter Tishler to share with you.
To: Individuals with Acute Porphyrias, who are Members of American Porphyria Foundation
Subject: Communication to us the benefits of your medications
Dear Folks,
I have established the American Porphyria Foundation Drug Database, for you all to consult for drug safety (or not) when you are prescribed a new medication. I received information from many of you several years ago, and added lots of your information to the Drug Database. I write you now to ask you to report me the names and results of any drugs you have been taking since the beginning of 2013, so that I can compare your report with the Drug Database and hopefully add new information (OK! or BAD!) to the Database.
Please complete the attached table and send it to the American Porphyria Foundation at 4900 Woodway Dr. Ste 780, Houston, TX 77056, or copy this table and send it back to us via Email. Many thanks!
Medication Name
Date Started
Stopped
Problem with Medication
No
Yes - Date
No
Yes - Nature of Problem
"Remember. Research is the key to your cure!"
BPA shares: 8 ways to better sleep
Wednesday - August 12, 2015 @ 10:30:01
8 ways to better sleep
Members often complain of poor sleeping patterns and a feeling of being tired all the time. Try some of the suggestions below to improve your quality of sleep.
1. Mattresses should be changed at least every 10 years. Quality deteriorates by up to 75%. Make sure you have the right mattress, test prospective beds by lying down in your normal sleeping position.
2. Cut out coffee. Reduce your intake of stimulants, including teas, coffee, cola and other caffeinated drinks, especially in the evening. Stick to milky drinks instead. More than one or two units of alcohol will also impair your quality of sleep.
3. Exercise more. Moderate physical activity lasting 20 minutes or more, three times a week, will help you sleep better and give you more energy. Because exercise is a physical stressor to the body, the brain compensates by increasing deep sleep. Light activity early in the evening is best.
4. Meditate. Use visualization or meditation or relaxing music to help you get off to sleep.
5. Dont Overheat. Bedroom temperature should be below 24C (75F) over this would greatly reduce the quality of your sleep.
6. Dont worry. Try to deal with your problems during the day. Confronting each difficult issue as it occurs should prevent all those niggling troubles from surfacing while you are trying to sleep.
7. Eat right. Certain types of food promote good sleep. Things such as leafy green vegetables, steamed or boiled; whole grains, mushrooms, and fruit. Avoid overly-rich foods just before bedtime.
8. Get up. If you cant sleep, dont just lie there, get up and make a hot milky drink, read a book or listen to soothing music until you feel drowsy again. Return to bed when your eyelids start feeling heavy and you start yawning.
Remember.Research is the key to your cure!"
Update: Caretaker Support Forum
Tuesday - August 11, 2015 @ 10:30:00
Caretaker Support Forum
New APF Caretaker Support Forum
Warren Hudson, who serves on the APF Board of Directors, has agreed to head our Caretaker Support Forum for spouses or partners who help their loved one cope with porphyria. To read more about Warrens story as a caretaker for a loved one with AIP click here.
The Caregiver Support Group strives to provide a forum to ask questions, share advice, experiences and provide a sounding board for those going through similar circumstances.
Our goal is to eventually provide multiple resources to assist caregivers in their day-to-day lives. This is your community and your input will help shape this service. Whether you are a spouse, partner, relative or friend of a porphyria patient, we want to hear from you. Contact the American Porphyria Foundation or email us at apfcaregiver@aol.com for more information.
We respectfully request that only caregivers of patients in the active process of diagnosis or with a diagnosis of a porphyria participate in this group.
"Remember.Research is the key to your cure!"
Stand up for your health!
Friday - August 7, 2015 @ 10:30:01
Are you sitting down reading this? You might want to stand up.Research shows sitting for extended periods may be hazardous to your health. British health experts are recommending office workers stand or do light activity for at least two hours a day. We all know someone who gets a good workout in every day, but then spends a large portion of their day sitting in front of a computer with few breaks. If your able to replace some of the sitting with light activity just getting up, moving around- taking the stairs, walk around your work place inside or out, maybe standing up when talking on the phone, walking down the hall instead of sending an email you can gain health benefits. So just don't sit there. Stand up, stretch move those muscles!
"Remember.Research is the key to your cure!"
APF NEWS!
Tuesday - August 4, 2015 @ 10:30:00
Is Your Membership Up to Date?
The fresh issue of the 3rd quarter Newsletter will hit your mailboxes in a few weeks! Make sure that your subscription and address is up to date! With you voluntary donations the APF is able to maintain our Newsletter, comprehensive physician and patient education programs and many other services. We do not receive government funding to run the APF, rather we receive donations from you, your friends, your family and people interested in the porphyrias. Please help us produce these materials!
Be A Medical Hero!
We are looking for 10 more patients-volunteers for the Phase 1 Alnylam Natural History Study. We are also enrolling patients to the EXPLORE trial, a prospective observational study of patients with acute hepatic porphyrias - including AIP, variegate porphyria, and hereditary coproporphyria - suffering from recurrent attacks.
With these studies, Alnylam and clinical investigators aim to learn more about the clinical course, management, and disease burden of patients with acute hepatic porphyrias that suffer from recurrent attacks.
Volunteering for research is the most important action you can take to change your future health because Research is the Key to Your Cure. You can be a Medical Hero and join many patients, who gave a day or more of their lives to help find important answers leading to new and improved treatments and a cure.
Please, contact the APF to get enrolled: 713.266.9617.
Amazon Smile :)
Please support the APF through the AmazonSmile program! Amazon will donate 0.5-0.8% of the price of your eligible purchases, at no cost to you.
7 Strategies to Developing a Positive Mental Attitude
Wednesday - July 29, 2015 @ 17:30:22
7 Strategies to Developing a Positive Mental Attitude
One of the best ways to increase your chance of success in all areas of life is to develop a positive mental attitude.
Taking a positive attitude toward life makes you a happier person all round, and one that other people in your life look up to, and want to spend time with.
Theres even evidence that having a positive attitude can help lower stress levels and improve your health.
Maintaining a Positive Mental Attitude
Here are 7 ways that we can all work toward developing a positive outlook on life.
1. Focus On the Present Mark Twain said,
Ive been through terrible things in my life, some of which actually happened.
He was pointing out the fact that we often add to our problems by building them up in our minds to be bigger than they really are.
How often do you find that things you worry about for days end up not happening at all, or not being as big a problem as you thought?
But, by focusing on the present as much as possible, you can minimize the worries and fears that lead to negative emotions.
2. Use Positive Language Do you ever notice how much of what you say is negative?
Some people constantly complain about the weather, their work, their spouse, their neighbors, and any number of other things.
We all do it from time to time.
However, its good to remind ourselves that our words are shaped by our thoughts, and the more we can look for positive things to say, the more positive our thoughts will become. Willie Nelson said it well when he said,
Once you replace negative thoughts with positive ones, youll start having positive results.
Make it your endeavor to commit to positive thinking. So, each day when you wake up give yourself a mini pep talk what do you want to achieve? How will you react to trying situations? How will you avoid negative thoughts? Remember, thinking positive is a habit, which means its possible to learn how to do it.
3. Accept When Things Arent Perfect It can be difficult to let go of the need for perfection and control in your life, but sometimes its very liberating to simply accept that things will not always go the way you hoped, and thats okay.
Sometimes things happen that are out of your control, and rather than wasting your energy on negative emotions, its better to just accept that things didnt go the way you planned or wanted.
Remember, most things pass with time.
4. Mix With Positive People Its a fact of human nature that we tend to mimic the people we spend the most time with.
Think of how teenagers tend to conform to the social code of their friends. Its the same for everyone else, too.
So, the more frequently you spend time with positive thinking people, the more likely it is that you will begin to think and act in a similar fashion.
Also, dont underestimate the power of laughing either, it has a wonderful way of reducing stress, connecting you with those around you, and generally making you feel better all round. I wholeheartedly agree with William James when he said,
We dont laugh because were happy, were happy because we laugh.
5. Contribute in A Meaningful Way one of the best ways to feel more positive is to contribute to your community in some way.
It can be tremendously uplifting to help others, whether its through the use of your time, skills or financial contributions.
As well as the good feelings that come with making a difference in someones life, contributing your time and effort to a cause, allows you a brief escape from your current problems, and perhaps may even allow you see your troubles in a different light.
6. Keep Learning Develop a curiosity about the world around you, and the people in it. No matter what situation youre in right now, there is always something we can learn from it.
Taking a real interest in life gives you energy, it helps create new ideas in your mind, and gives you a different way of thinking about things, that can have a positive impact on your life as a whole.
7. Be Grateful Spend a little time each day thinking of things that you are truly thankful for in your life.
Reminding yourself of all the reasons you have to be grateful, helps to maintain some focus on your situation.
Being thankful will often turn initial anger or frustration into something more positive. Remember, we all have weaknesses, but focusing on your strengths prevents them getting the better of us.
A good practice to get into is that of keeping a gratitude journal. This is where you make a note of at least 5 things that make you happy or thankful each day. This is one of the best ways to foster the habit of gratitude.
Finally, keep in mind that how you view your life is your choice. No one is forcing you to have a negative attitude, so take control and change it for a happier, more energetic, and more enthusiastic life.
"Remember.Research is the key to your cure!"
Alnylam and Collaborators Publish Pre-Clinical Results with ALN-AS1, an RNAi Therapeutic Targeting Aminolevulinic Acid Synthase-1 (ALAS-1) for the Treatment of Hepatic Porphyrias, in the Proceedings of the National Academy of Sciences
Friday - July 24, 2015 @ 10:30:02
We need research volunteers, if you have an Acute Porphyria and would like more information on this and other studies please contact Natalia APF 1-866-APF-3635
Alnylam and Collaborators Publish Pre-Clinical Results with ALN-AS1, an RNAi Therapeutic Targeting Aminolevulinic Acid Synthase-1 (ALAS-1) for the Treatment of Hepatic Porphyrias, in the Proceedings of the National Academy of Sciences
05.21.2014
- New Paper Documents Previously Presented Proof-of-Concept Results in Mouse Model of Acute Intermittent Porphyria (AIP) -
- RNAi Therapeutics Targeting ALAS-1 Completely Block Production of Toxic Heme Biosynthesis Intermediates that Cause Symptoms and Disease Pathology -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the publication in the Proceedings of the National Academy of Sciences (PNAS) of pre-clinical results with RNAi therapeutics targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic porphyrias, including acute intermittent porphyria (AIP). In the paper, titled "RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice," Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai in New York City documented results from pre-clinical models of the human disease showing that RNAi therapeutics targeting ALAS-1 can completely block the abnormal production of toxic intermediates of the heme biosynthesis pathway that cause the symptoms and disease pathology of AIP. This new paper provides proof of concept for an RNAi therapeutic for the treatment of AIP.
"Our data in a mouse model of AIP, now published in PNAS, demonstrate that RNAi therapeutics targeting ALAS-1 can achieve potent, rapid, and durable suppression of the toxic heme biosynthesis intermediates that cause the symptoms and disease pathology of AIP. As such, these findings provide key pre-clinical proof-of-concept data for our ALN-AS1 program. We believe ALN-AS1 has the potential to be a transformative therapy for patients with hepatic porphyrias including AIP, an ultra-rare genetic disease with enormous unmet medical need," said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development of Alnylam. "We are currently advancing our Development Candidate for ALN-AS1, which employs our Enhanced Stabilization Chemistry-GalNAc-conjugate technology. This technology enables subcutaneous dosing with improved potency and durability, and a wide therapeutic index, and is now clinically validated based on results from our hemophilia program. We are on track to file an Investigational New Drug application for ALN-AS1 in late 2014 or early 2015, and look forward to advancing this investigational medicine to patients."
The acute hepatic porphyrias, including AIP, are ultra-rare orphan diseases caused by loss-of-function mutations in enzymes involved in heme biosynthesis, leading to accumulation of toxic heme intermediate precursors. In the case of AIP, there are approximately 5,000 patients in the U.S. and Europe that suffer acute, life-threatening porphyria attacks every year; there are approximately 500 patients afflicted with recurrent debilitating attacks, often occurring once per month. Treatment options for AIP patients suffering from an attack are limited, and include the use of heme preparations that show limited efficacy and are associated with a number of complications including phlebitis, iron overload, and infections related to the need for central venous access in some patients. Currently, there are no approved drugs available to prevent attacks from occurring. Alnylam's approach is to knock down ALAS-1, an enzyme upstream of porphobilinogen deaminase (PBGD), the defective gene in AIP. RNAi-mediated silencing of hepatocyte ALAS-1 could reduce the abnormal production of the toxic heme intermediates, specifically aminolevulinic acid (ALA) and porphobilinogen (PBG), which mediate the symptoms and disease pathology in AIP patients as well as in some of the other acute hepatic porphyrias. Alnylam believes that a subcutaneously administered RNAi therapeutic targeting ALAS-1 has the potential to be used as a prophylactic approach to prevent attacks, and also as a therapy for acute attacks.
In the new paper published in PNAS, Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai documented their results from studies performed in a mouse model of AIP. Prophylactic administration of an ALAS-1 specific siRNA completely protected AIP mice from phenobarbital-induced up-regulation of hepatic ALAS-1 mRNA and protein, as well as the resulting accumulation of the neurotoxic ALA and PBG heme biosynthesis precursors. This protective effect was dose responsive and durable, with a single dose administration resulting in a protective effect that lasted for at least two weeks. This feature provides an advantage over prophylactic hemin - the current standard of care in AIP - which is infused as often as twice a week in patients with frequent attacks. Further, in a treatment model, a single dose of ALAS-1 siRNA rapidly reduced the high levels of plasma ALA and PBG that were elevated during a phenobarbital-induced acute attack. In addition, preliminary comparative studies show that ALAS-1 siRNA administration was more effective than heme administration in the treatment of an acute attack, as seen by the more extensive and rapid lowering of both ALA and PBG with its administration. New results from rotarod studies showed that treatment with an ALAS-1 siRNA was associated with a significant improvement in performance as compared with animals treated with a control siRNA, suggesting that treatment with the drug can protect against symptoms of neuromotor impairment associated with AIP attacks. Finally, data were shown demonstrating that administration of ALAS-1 siRNA was not associated with a hepatic heme deficiency or altered liver hemoprotein activity.
"AIP is caused by an inherited deficiency in porphobilinogen deaminase that can result in accumulation of toxic intermediates in the heme biosynthesis pathway. Patients with AIP present with acute, and at times recurrent attacks that are characterized by severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, and in very severe cases paralysis and respiratory failure," said Robert J. Desnick, M.D., Ph.D., Dean for Genetics and Genomic Medicine and Professor and Chair Emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City. "Our pre-clinical work in a mouse model of AIP has shown that RNAi-mediated silencing of ALAS-1 results in rapid and effective normalization of the toxic heme biosynthesis intermediates ALA and PBG that cause the symptoms and pathophysiology of the disease. In addition, treatment with ALAS-1 siRNA in the model led to more rapid and effective lowering of ALA and PBG than a single hemin infusion, which is the standard of care for patients who have acute hepatic porphyria attacks. We have also now shown that RNAi knockdown of ALAS-1 improves the neuromotor impairment associated with acute attacks, and is not associated with a hepatic heme deficiency."
"RNAi therapeutics are promising as a novel treatment for AIP, and the other acute hepatic porphyrias, where there is a clear need for new therapies," said Makiko Yasuda, M.D., Ph.D., Assistant Professor in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City. "We look forward to continuing our very close collaborative efforts with Alnylam on the advancement of this program to the clinic."
Alnylam is currently advancing ALN-AS1, a subcutaneously administered RNAi therapeutic targeting ALAS-1 for the treatment of porphyria, including AIP. ALN-AS1 utilizes the company's proprietary Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index. ESC-GalNAc conjugates are a clinically validated platform based on recent results from the company's ALN-AT3 program in a Phase 1 study. At the 9th Annual Meeting of the Oligonucleotide Therapeutics Society in October 2013, the company presented results in non-human primates (NHP), showing that multi-dose administration of an ESC-GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA in NHPs, with an ED50 of approximately 1.25 mg/kg. Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of PBG and ALA, the toxic heme intermediates in AIP. Alnylam is currently conducting additional studies with ALN-AS1 and expects to file an Investigational New Drug (IND) application or IND equivalent in late 2014 or early 2015.
Dr. Robert Desnick and Dr. Makiko Yasuda are named with Alnylam Pharmaceuticals as co-inventors on a pending patent covering compositions and methods for inhibiting the ALAS-1 gene. In addition, Dr. Desnick receives financial compensation as a consultant for Alnylam Pharmaceuticals, and owns equity in Alnylam Pharmaceuticals in the form of stock options.
About Acute Intermittent Porphyria
Acute intermittent porphyria (AIP) is an ultra-rare autosomal dominant disease caused by loss-of-function mutations in porphobilinogen deaminase (PBGD), an enzyme in the heme biosynthesis pathway. Exposure of AIP patients to certain drugs, dieting, or hormonal changes can trigger strong induction of aminolevulinic acid synthase-1 (ALAS-1), another enzyme in the heme biosynthesis pathway, which can lead to accumulation of heme intermediates upstream of PBGD that precipitate attack symptoms. Patients with AIP can suffer acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, and possibly death if left untreated. Approximately 5,000 patients in the U.S. and Europe suffer acute porphyria attacks annually, and approximately 500 patients are afflicted with recurrent debilitating attacks. Treatment options for AIP patients suffering from an acute attack are limited; patients are treated with intravenous heme analogues that have a slow onset and can result in severe thrombophlebitis and iron overload. Currently there is no approved prophylactic treatment available to prevent recurrent attacks, which often occur monthly in women associated with menses. There exists a significant need for therapies for AIP patients.
About GalNAc Conjugates and Enhanced Stabilization Chemistry (ESC)-GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index. This delivery platform is being employed in several of Alnylam's genetic medicine programs, including programs in clinical development.
About LNP
Alnylam has licenses to Tekmira LNP intellectual property for use in RNAi therapeutic products using LNP technology.
About RNAi
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics as genetic medicines, including programs as part of the company's "Alnylam 5x15TM" product strategy. Alnylam's genetic medicine programs are RNAi therapeutics directed toward genetically defined targets for the treatment of serious, life-threatening diseases with limited treatment options for patients and their caregivers. These include: patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR for the treatment of ATTR in patients with TTR cardiac amyloidosis, including familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-CC5, an RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, an RNAi therapeutic targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia; and other programs yet to be disclosed. As part of its "Alnylam 5x15" strategy, as updated in early 2014, the company expects to have six to seven genetic medicine product candidates in clinical development - including at least two programs in Phase 3 and five to six programs with human proof of concept - by the end of 2015. Alnylam is also developing ALN-HBV, an RNAi therapeutic targeting the hepatitis B virus (HBV) genome for the treatment of HBV infection. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In March 2014, Alnylam acquired Sirna Therapeutics, a wholly owned subsidiary of Merck. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, the New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.
About "Alnylam 5x15â?¢" and Genetic Medicines
The "Alnylam 5x15" strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics as genetic medicines. Alnylam's genetic medicine programs are RNAi therapeutics directed toward genetically defined targets for the treatment of diseases with high unmet medical need. These programs share several key characteristics including: a genetically defined target and disease expressed in the liver; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi platform with clinically proven delivery to the liver; the opportunity to monitor an early biomarker in Phase 1 clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. As updated in early 2014, the company expects to have six to seven genetic medicine product candidates in clinical development - including at least two programs in Phase 3 and five to six programs with human proof of concept - by the end of 2015. The "Alnylam 5x15" programs include: patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) in development for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR in development for the treatment of ATTR in patients with TTR cardiac amyloidosis, including familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) in development for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-CC5, an RNAi therapeutic targeting complement component C5 in development for the treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting aminolevulinic acid synthase-1 (ALAS-1) in development for the treatment of hepatic porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 in development for the treatment of hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 in development for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, a subcutaneously administered RNAi therapeutic targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia; and other programs yet to be disclosed. In 2014, Alnylam and Genzyme, a Sanofi company, formed a multi-product geographic alliance on Alnylam's genetic medicine programs. Specifically, Alnylam will lead development and commercialization of programs in North America and Europe, while Genzyme will develop and commercialize products in the rest of world. In addition, Alnylam and Genzyme will co-develop and co-commercialize ALN-TTRsc in North America andEurope.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-AS1 for the treatment of porphyria including acute intermittent porphyria (AIP), its expectations with respect to timing, and success of its clinical trials, including with ALN-AS1, its expectations regarding the potential market opportunity for ALN-AS1, its expectations regarding its "Alnylam 5x15" product strategy, and its plans regarding commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to manage operating expenses, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation to update any forward-looking statements.
Thank you each and every member of the APF. We could not do it without YOU!
Thursday - July 23, 2015 @ 16:50:22
Thank you each and every member of the APF.
We could not do it without YOU!
Look at all the research projects, advancements toward new medications, and people living long healthier lives. Thank you for getting the word out to your Doctors, RN's, Family and Friends.
To the hospitals, ED's, Dr. offices with your Patient packets, Doctors receiving the Dr Kits and ER Kits. We need you to continue speaking up about Porphyria how are you affected daily by it.
Look at all the media attention all around the world- keep speaking up and out loud!
Take a minute and ask yourself where did I get this information from, have I myself read it and educate myself and loved ones to. I enjoy receiving gifts "golden nuggets" of information from the APF.
I make sure that I once a year or more, I make sure that my membership is current to continue to receive these gifts & my donations are tax deductible. So will you help encourage your family, friends by donating your time, efforts, and monetary donations to continue to support the APF. If you have just 5 minutes a simple phone call will do so much good. Please call 1-866-APF-3635 and have a wonderful weekend to all.
"Remember.Research is the key to your cure!"
THE "MOVE IT IN THE MOONLIGHT RUN" In Bulngton, NC August 28, 2015
Monday - July 20, 2015 @ 10:30:02
THE "MOVE IT IN THE MOONLIGHT RUN" In Bulngton, NC August 28, 2015
Shawn Willis is a dynamo in everything he undertakes. He is the owner of the Chick-Fil-A stores in Burlington, NC. On August 28, Shawn hosts the MOVE IT Moonlight Run from for porphyria awareness to help fund the APF educational programs. Please follow the event details and join the run:http://cfaraceseries.com/races/161/
"Remember.Research is the key to your cure!"
Information on FB Australia Site: www.porphyria-australia.org/
Friday - July 17, 2015 @ 15:55:09
If you are trying to locate a good Doctor in Australia or the Australian Porphyria Group Please note this information below. On FB you can contact with Jennifer Bellerridge and visit: http://www.porphyria-australia.org/ For Testing Locations see below:
Dr Victor Poulos and A/Prof Peter Stewart NSW Porphyria Reference Unit Biochemistry Department, ROYAL PRINCE ALFRED HOSPTAL Missenden Rd Camperdown NSW Australia 2050
Porphyrin Reference Laboratory, Biochemistry Department, ROYAL MELBOURNE HOSPTAL, Cnr Grattan Street and Royal Parade, Parkville, 3050.
Phone: (61-3) 9342 7641
This is the only recognised porphyria testing laboratory in Victoria.Samples can be collected and forwarded by commercial laboratories provided they follow the recommendations.
SOUTH AUSTRALIA
John Zoanetti Senior Medical Scientist, Department of Genetic Medicine WOMEN'S AND CHILDREN'S HOSPITAL 72 King William Road, North Adelaide, SA 5006
Phone: (61-8) 8161 6732 Fax: (61-8) 8161 7100
WESTERN AUSTRALIA
Dr Ric Rossi PATHWEST Locked Bag 2009 Nedlands, 6909, W.A.
Phone: (61-8) 9346 2845 Fax: (61-8) 9346 3882
WELCOME all new members!
Friday - July 17, 2015 @ 15:10:43
WELCOME all new members!
Were so happy to have you all here.
The APF has been very busy with research studies and we encourage you to please contact the APF about getting registered, if we want a cure we need YOU! Ask for Natalia Apf, Jessica Apf @ 1-866-APF-3635
If you would like to join the Purple Light Blog it is complimentary to join. Learn how to handle stree and anxiety while you are sick. How to have a great Doctors visit, being prepared to diet and exercise. So join today at this link: https://www.blogger.com
Have a wonderful summer weekend everyone!
Your APF Membership & Support the APF with AmazonSmile for Charitable Organizations!
Wednesday - July 15, 2015 @ 10:30:00
Your APF Membership
We are currently working on the 4th quarter Newsletter, where you can find latest news, updates and stories from the porphyria world. Our members, who made deductible charitable contributions, will receive the fresh issue.
The APF is able to maintain our physician and patient education programs and many other services because of your support. Since we do not receive government funding, we need your support and donations. Is your membership and contact information up to date? If you have moved, please update us with your current address. Be sure to send us your email address so you can receive the E-news.
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You can also support the APF through the AmazonSmile program! Amazon will donate 0.5-0.8% of the price of your eligible purchases to us, at no cost to you. Please make us your choice of a charitable organization, support the research while shopping!
Please note, the program will only be available to shoppers who visit Amazon via a special web address - smile.amazon.com - instead of the normal Amazon.com homepage.
It is easy and free, AmazonSmile is the same Amazon you know. Same products, same prices, same service. Thank you for supporting us!
Important Post *** Tests for Porphyria Diagnosis***
Tuesday - July 14, 2015 @ 16:51:39
Tests for Porphyria diagnosis
The porphyrin precursors ALA and PBG and porphyrins are readily measured in urine. Normal urine contains appreciable amounts of these substances, and different individuals may have widely different levels. It must also be remembered that "normal ranges" do not necessarily include all normal people. Therefore, small increases, especially in porphyrins, are not always significant.
ALA is an amino acid, and PBG is a pyrrole. Both are colorless, but when present in large amounts in a solution such as urine, PBG can spontaneously form uroporphyrin, which is reddish, and other products that are brownish.
The Mauzerall-Granick method and variations of that method are preferred for measuring ALA and PBG and have been available for many years. The test involves first separating ALA and PBG from each other and from interfering substances in urine, and converting ALA to a pyrrole. Ehrlich's reagent, which reacts with pyrroles (and some other chemicals) to make a colored substance that is readily seen, is added, and the color is measured separately for both ALA and PBG with an instrument called a spectrophotometer. The Watson-Schwartz test and the Hoesch test are qualitative tests (result either positive or negative) for PBG that also use Ehrlich's reagent; they may lead to false positive results if the person doing the test lacks experience in interpretation. These two tests are rarely used if at all. If a qualitative test is positive, a quantitative assay should be done later on the same sample.
Because PBG is generally so strikingly increased during an attack of acute Porphyria, quantitation even on a spot sample (rather than a 24 hour collection) is highly informative. Requiring a 24 hour urine collection for quantitative measurements during an attack may result in considerable delay in confirming the diagnosis. Furthermore, ALA and PBG may drop considerably (especially in HCP and VP) if there is a delay of several days in collecting a 24 hour urine.
In HCP and VP, urinary porphyrins generally remain increased longer after an acute attack than do ALA and PBG. Therefore, screening for acute porphyrias should probably include measurement of total urinary porphyrins. However, it needs to be kept in mind that nonspecific increases in urinary porphyrins are common.
Measurement of PBG in serum is useful when acute Porphyria is suspected and urine cannot be collectedfor example in patients with kidney failure. Serum PBG is increased in serum in the acute porphyrias, although when kidney function is normal, the concentrations are lower than in urine.
Porphyrins are tetrapyrroles (composed of four pyrroles). Porphyrins in their oxidized forms are reddish in color and are also fluorescent. Fluorescent substances, when exposed to light at certain wavelengths, emit light with a different wavelength. Porphyrins appear intensely red when exposed to long-wave ultraviolet light (UV-A). This makes them visible with a Wood's lamp, and enables them to be measured accurately with a spectrofluorometer. Within cells, all porphyrins that are intermediates in the heme biosynthetic pathway, with one exception, are in the reduced form, and are colorless and nonfluorescent. The last intermediate, protoporphyrin, is an oxidized porphyrin. Porphyrins that leave the cells and appear in blood, urine and feces are mostly oxidized and appear reddish to the naked eye and are fluorescent.
The total amount of porphyrins in a urine sample is easily measured. This is a useful test for screening especially when combined with ALA and PBG. But an increase in urine porphyrins is nonspecific, and may not be an indication of an acute Porphyria if ALA and PBG are normal.
A variety of porphyrins are present in urine. When there is an increase, particularly a large increase, in total urine porphyrins, it is often useful to determine the individual porphyrins found in urine. It is seldom important to do this if the total in normal.
The most common method for separating the individual porphyrins is "high performance liquid chromatography" (HPLC). This method will measure amounts of porphyrins with 4 or more carboxyl groups found in urine (see Table 3). In interpreting HPLC results, it is most useful to see which porphyrins predominate rather than focus on the amounts of each porphyrin.
Table 3. Porphyrin names and the corresponding number of carboxyl groups
Carboxyl groups make the porphyrin more soluble in water. Porphyrins with less than 4 carboxyl groups are not found in appreciable amounts in urine. The less soluble porphyrins with 2-3 carboxyl groups are excreted mostly in bile and feces. Coproporphyrin is excreted by both routes.
Porphyrin names Number of carboxyl groups Uroporphyrin (octacarboxyl porphyrin) 8 Heptacarboxyl porphyrin 7 Hexacarboxyl porphyrin 6 Pentacarboxyl porphyrin 5 Coproporphyrin (tetracarboxyl porphyrin) 4 Harderoporphyrin (tricarboxyl porphyrin) 3 Protoporphyrin (dicarboxyl porphyrin) 2 Coproporphyrin predominates in normal urine. An increase in total urine porphyrins with a predominance of coproporphyrin is seen especially in HCP and VP. But this finding alone is very nonspecific, because increases in urine porphyrins and especially coproporphyrin are common in many medical conditions such as liver diseases, bone marrow disorders and lead poisoning. Therefore, increases in urine coproporphyrin are often not due to Porphyria.
When total urine porphyrins are increased due to PCT or HEP, the increase is predominantly accounted for by uroporphyrin and heptacarboxyl porphyrin. Hexa- and pentacarboxyl porphyrin are increased to a lesser degree. These increases are understandable, because the corresponding reduced porphyrins are, in sequence, substrates for UROD, the enzyme that is deficient in PCT and HEP (Table 1). The enzyme removes 4 carboxyl groups from uroporphyrinogen one at a time to form coproporphyrinogen. Therefore, uroporphyrinogen and the intermediates with 7, 6, and 5 carboxyl groups also accumulate when the enzyme is markedly deficient. Adding to the complexity of the porphyrins in PCT is a series of porphyrins called isocoproporphyrins, which result from the next enzyme in the pathway acting on pentacarboxyl porphyrin.
The body makes primarily the isomer III type of porphyrinogens, because only these are precursors of heme. But some isomer I porphyrinogens are made in small amounts and are excreted. HPLC detects the different isomers, which adds even greater complexity. The isomer I porphyrins predominate in urine (as well as erythrocytes, plasma and feces) in CEP, because of the marked deficiency of the enzyme UROS.
Sodium carbonate (5 grams, added to a 24 hour urine bottle prior to collection) is widely recommended for urine specimens intended for measurement of PBG and porphyrins. It is widely recommended that acid be added to containers for collection of urine in which ALA is to be measured, because ALA is more stable in acid. This may be suitable if only ALA is to be measured as, for example, in screening for lead poisoning. Unfortunately, acid conditions enhance degradation of PBG, and it is seldom important to measure only ALA. Therefore, if Porphyria is suspected, sodium carbonate rather than an acid should be used, because it will be important to measure PBG and possibly porphyrins, as well as ALA, in the sample.
Fecal Porphyrins
Total fecal porphyrins are markedly increased especially in active HCP and VP and to a lesser extent in PCT and EPP. Fecal porphyrins can be separated and measured individually by HPLC. Porphyrins with 2-4 carboxyl groups generally predominate in feces. These are excreted by the liver into the bile and then flow into the intestine.
As with urine, it is most useful to measure the total amount of porphyrins in a fecal sample. If this is increased, then the laboratory should determine by HPLC which porphyrins predominate rather than focus on the amount of each porphyrin. Fecal porphyrin determinations may be confounded by variations in fecal flow; most people have one or a few bowel movements daily and a "24 hour stool collection" is really not uniform from day to day. Substances in the diet and any internal bleeding into the stomach or intestines may also interfere.
Blood testsplasma or serum
Plasma (or serum) total porphyrins. Normally there are only trace amounts of porphyrins in plasma, and the amounts increase markedly in patients with cutaneous porphyrias. This is a very useful and underutilized test when a porphyria is suspected as a cause of photosensitivity. Being both sensitive and specific, it is increased in any patient with skin problems related to any type of Porphyria and is seldom increased in other conditions.
The preferred method, at least for screening, involves diluting plasma with a nonacid, neutral buffer and measuring the porphyrins directly by fluorescence scanning. This can serve not only as a rapid screening method for all cutaneous porphyrias but can determine whether a patient has VP rather then PCT and other porphyrias that can cause blistering skin lesions. This method also detects some cases of latent VP.
The excess porphyrins in plasma in VP are mostly covalently linked to plasma proteins and are readily detected by this method but may not be detected by the HPLC methods. It needs to be kept in mind that the normal range for plasma porphyrins is higher in patients with end-stage renal disease. Moreover, hemolysis of a blood sample invalidates a plasma porphyrin determination, because normal erythrocytes contain much larger amounts of porphyrin (in the form of Zn protoporphyrin) than does normal plasma. When the total plasma porphyrin is increased, HPLC can be used to determine which porphyrins predominate. This is done less commonly than for urine.
Plasma porphyrin measurements may be less useful for detecting EPP than other cutaneous porphyrias. One reason for this may be that protoporphyrin is very light sensitive, and the concentration in the sample can decrease rapidly if it is exposed to light during processing. Therefore, erythrocyte porphyrins should be measured if EPP is strongly suspected.
Blood testserythrocytes
Erythrocyte porphyrins. Normal erythrocytes, in contrast to plasma, contain appreciable amounts of porphyrins. This is almost all protoporphyrin. Therefore, erythrocyte porphyrin measurements are customarily reported as erythrocyte protoporphyrin. However, the methods can detect other porphyrins and would be more accurately described as measuring total erythrocyte porphyrins.
Because increases in erythrocyte porphyrins always almost are due to increased protoporphyrin, it is seldom necessary to separate the porphyrins in erythrocytes by HPLC. In CEP, however, isomer I uroporphyrin and coproporphyrin are usually the predominant porphyrins, as can be demonstrated by HPLC.
The protoporphyrin normally found in erythrocytes is complexed with zinc (Zn) as Zn protoporphyrin. Zn protoporphyrin increases in many conditions other than porphyrias, including iron deficiency, lead poisoning and almost any type of disorder that affects erythrocytes. Therefore, increases in erythrocyte porphyrins are not specific for porphyrias. The only condition in which free protoporphyrin (not complexed with Zn) is increased is EPP. An increased erythrocyte protoporphyrin can be shown to be due to free protoporphyrin by a simple procedure called ethanol extraction. This is useful for confirming a diagnosis of EPP.
Erythrocyte enzymes
Assays for heme biosynthetic pathway enzymes in erythrocytes, especially ALAD, PBGD and UROD, have become widely available. These assays should not be used as first-line tests for porphyrias when screening patients with symptoms. They are useful for family studies, when it is established that an index case has a particular enzyme deficiency. Difficulties with these assays in clinical practice include the following: (i) Ranges for a particular Porphyria and normals may overlap. (ii) Some mutations may cause a particular enzyme to be deficient only in nonerythroid tissues. (iii) Falsely low values are common due to problems with collecting or transporting the sample. Some laboratories employ coupled enzyme assays that may lack specificity. If a patient is found to have a deficiency of more than one enzyme in erythrocytes, it is likely that the results are not reliable.
DNA tests
Specific mutations can be identified by DNA testing. This may be the ultimate means of confirming a diagnosis of Porphyria. Once a mutation is identified in a family, this is the most reliable means of detecting other carriers of the same porphyria associated mutation.
Not every family with a given type of porphyria has the same mutation. For example, more than 200 different mutations have been identified in the PBGD gene in different AIP families. No single test for all of these DNA variations is available. Therefore, DNA testing is not suitable for screening for porphyrias, except within families.
Furthermore, not all DNA variations cause the enzyme product to be impaired and lead to a disease. Therefore, a new mutation requires further research work in the laboratory to show that it impairs the enzyme product. For these reasons, DNA testing is most meaningful only after standard testing for Porphyria has confirmed a diagnosis.
"Remember.Research is the key to your cure!"
Sign Up Today for Our Patient Advocacy Summit Information Session Webinar Global Genes
Monday - July 13, 2015 @ 16:36:02
Sign Up Today for Our Patient Advocacy Summit Information Session Webinar July 15, 2015 - 2:00 pm PT / 5:00 pm ET Register here for the information session.
Find out what you need to know about attending the RARE Patient Advocacy Summit on September 24/25, 2015, either in person or via livestream webcast by attending our information session webinar. You'll learn more about the topics we are covering, speakers, logistics, and a sneak peek of upcoming programs for Foundation Alliance partners and patients.
Connect. Educate. Engage. Achieve.
Nicole Boice, Global Genes CEO, and Kym Kilbourne, VP of Advocacy, will be sharing more details about our summit's jam-packed agenda, registration information, and how to participate live via livestream if you are not able to make it in person. They will also be available to answer any questions you may have regarding the summit and our Tribute to Champions of Hope Gala.
If you have been recently diagnosed, are building a disease community, thinking about funding early research, actively engaged in developing a treatment, or have been advocating in rare disease for decades this is the meeting you need to attend!
If you are not able to make it at the time above, please register here, and we will send you the slides and recorded webinar that you may view at a later time.
I am very pleased and proud to announce that by a vote of 344-77, the United States House of Representatives passed the 21st Century Cures Act (H.R. 6), which aims to accelerate the discovery, development and delivery of life-saving and life-improving therapies. The bill also would transform the quest for faster cures by modernizing and removing regulatory processes and barriers that often slow the translation of new discoveries into treatments for patients.
The APF has been very involved in the promotion of the passing of this bill. We thank those of you who contacted your Congressmen in support of this legislation.
Desiree
APF Executive Director
"Remember.Research is the key to your cure!"
Media Attention EPP PATIENTS WANTED 1000
Wednesday - July 8, 2015 @ 10:30:00
Media Attention
We would like to thank all EPP patients and family members who have been able to bring their stories to federal and local TV and print media.
Please contact your local radio stations, TV channels and newspapers if you haven't done it yet and share your story about your type of porphyria! If you need any assistance, supplies or awareness materials give us a call at 713.266.9617.
****ATTENTION!**** The APF is looking for at least 1,000 EPP patients NOW! We are organizing a giant push for the FDA. Please message me your name, address, and email address or call the APF office at 1-866-APF-3635. Thank you all!
"Remember.Research is the key to your cure!"
Can positive thinking make you well?
Monday - July 6, 2015 @ 16:21:59
I enjoyed reading this over I hope that you do to. I think you can insert PORPHYRIA DISEASE in there.
Can positive thinking make you well?
By Deepak Chopra, Special to CNN
Updated 6:10 PM ET, Mon December 5, 2011
There is much to be gained and no risks involved in trying to reach the best state of mind possible, the author says.
Story highlights
Studies show contradicting data on whether positive thinking can aid health
Deepak Chopra: Placebo effect proves thinking is medicine and can be helpful if done properly
The real point isn't to rescue a dying patient but to maintain wellness, Chopra says
Observers may have noticed recently that mainstream medicine is taking a harder line against positive thinking.
Surveys of the leading research in the field conclude that recovery rates from cancer, for example, are not higher among patients who take a positive attitude about fighting their disease. Studies that show the reverse have been small and, according to their critics, flawed in serious ways.
Anyone would be forgiven for throwing up their hands. This seems like another example of dueling data, where one study's findings are contradicted by the next study, leaving the public in a state of confusion.
Doctors are confused, too. It has always been part of a doctor's kit bag to tell patients to keep their spirits up. Until a few decades ago, it was standard not to acquaint a dying patient with the gravity of his condition, which implies an unspoken agreement that hearing bad news isn't good for patients.
At the same time, doctors want to protect their profession, so few want to cross the line and support the notion that how you think can work as powerfully as "real" medicine.
Let's see if some of this confusion can be cleared up.
First of all, thinking is "real" medicine, as proven by the placebo effect. When given a sugar pill in place of a prescription drug, an average of 30% of subjects will show a positive response. What causes this response isn't a physical substance but the activity of the mind-body connection. Expectations are powerful. If you think you've been given a drug that will make you better, often that is enough to make you better.
Deepak Chopra says there can be no denying that the mind-body connection is powerful.
This implies that a person should be able to trigger the placebo effect on himself. However, there is a psychological illusion involved. Take away the authority figure in a white coat to tell you that you are taking an effective drug, and suddenly the sugar pill is just a sugar pill. You can't fool yourself when you know what the placebo is.
This can't be the whole story, however. We can't deny that the mind-body connection is powerful. So is there a placebo effect that doesn't involve fooling the patient? Can you trigger your own inner defenses by the way you think?
Those who believe in positive thinking say yes. I believe the situation is more nuanced. On the plus side, the studies that debunk positive thinking deal with very sick patients struggling to recover from major diseases. They do not comment on how positive thinking might prevent disease or how it might affect someone in the very early stages of illness.
The real point isn't to rescue a dying patient but to maintain wellness.
Does positive thinking keep you well? Right now the camps are divided, because with the rise of genetics, many disorders clearly have triggers that originate in our genes.
In the public's mind, being told that cancer or diabetes is genetic acts as final authority. Luckily for the positive-thinking camp, this fatalistic attitude is mistaken. Genes are dynamic, not fixed; they respond to a person's environment, behavior and attitudes. Indeed, a now-famous study in Sweden showed that a tendency to diabetes may be strongly affected by the diet your great-grandfather ate. A whole new field is studying how much choice we have at the genetic level.
The findings are not complete by any means, yet there is no harm in assuming that your mind affects your genes, because there is abundant evidence to support this attitude.
Medicine hasn't proven that positivity is good prevention, but let's go a step further. To me, the problem with positive thinking is the thinking part. It takes effort to be positive all the time. The mind has to defend itself from negativity, and that is exhausting as well as unrealistic. You may succeed in calming the appearance you present to the world, but there's almost always a struggle hidden just below the surface; at the very least there is a good deal of denial. Being fanatically positive is still fanaticism.
The alternative to thinking is a calm mind that is at peace with itself. I believe that such a mind delivers the benefits that positive thinking cannot, and my view is supported by studies showing a decline in high blood pressure, stress levels and other disease states among long-term meditators.
Meditation is a spiritual practice, but it's also a mind-body practice. Here the results are not final, either, in part because almost the only research subjects tend to be Buddhist monks. We need expanded studies based on Western subjects; that much is clear.
The upshot is that medicine cannot be definitive on how mood affects wellness. But if I wanted to enhance a state of wellness before symptoms of illness appeared, there is much to be gained and no risks involved in trying to reach the best state of mind possible.
"Remember. Research is the key to your cure!"
A Note from the APF: Desiree Lyons~
Friday - July 3, 2015 @ 16:59:12
A Note from the APF: Desiree Lyons~
Hi all, The APF is facilitating research. One research trial is very easy. It is called the Longitudinal Study because you will answer questions over a few years. All you have to do is talk with a research team member and answer their questions and answer an extensive questionnaire. This is your chance to tell everything you want Drs to know about YOUR porphyria.
You don't have to fly anywhere. We need you badly. The more ppl who participate, the more the government sees the number of people who have porphyria and can determine a real incidence rate. This in turn leads to more research funding. . Call the APF office and be put together with a research coordinator at a porphyria research center.
This is so easy. Everyone should be doing this. Research is the key to our cure. Apf staff, Natalia and Jessica , will tell you about other research opportunities. . Toll free. 866.APF.3635. Or save the APF funds by calling 713.266.9617
Please do today .
"Remember. Research is the key to your cure!"
ABC Nightline EPP and Dr. Desnick
Friday - June 26, 2015 @ 10:30:00
ABC Nightline EPP and Dr. Desnick
The APF was able to secure another show on EPP. Don't miss the ABC Nightline Episode tonight featuring the Fulkerson family and Dr. Robert Desnick. More info: http://abcnews.go.com/Nightline
We have received a great deal of media attention within the last month. We had several major TV programs: Discovery Life "Diagnose Me" covering AIP and NBC "Dateline: Out of the Shadows" covering EPP. We also had a show on ABC "Good Morning America" and on Telemundo channel.
Thank you for sharing links, news and educating society on porphyrias. All the media attention has been greatly helped enhance porphyria education and awareness.
"Remember. Research is the key to your cure!"
Press Release for Acute Type Porphyria and Research: From Alnylam Phase 1 Clinical Trial Drug
Wednesday - June 24, 2015 @ 10:30:02
Press Release for Acute Type Porphyria and Research: From Alnylam Phase 1 Clinical Trial Drug
Alnylam Initiates Phase 1 Clinical Trial for ALN-AS1, an Investigational RNAi Therapeutic Targeting Aminolevulinic Acid Synthase 1 (ALAS1) for the Treatment of Acute Hepatic Porphyrias, Including Acute Intermittent Porphyria (AIP)
05.26.2015
- Company Expects to Present Initial Clinical Results in Early 2016 -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it has initiated a Phase 1 clinical trial with ALN-AS1, a subcutaneously administered investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias, including acute intermittent porphyria (AIP). The Phase 1 trial of ALN-AS1 will be conducted initially in AIP patients who are asymptomatic "high excreters" (ASHE). These ASHE subjects have a defined mutation in the porphobilinogen deaminase (PBGD) gene and elevated urinary levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), but do not have a current history of porphyria attacks or disease activity. Subsequently, the trial is designed to enroll AIP patients who experience recurrent porphyria attacks. The company expects to present initial clinical data from this trial in early 2016.
"We believe ALN-AS1 has the potential to be a transformative therapy for patients with acute hepatic porphyrias, a group of ultra-rare monogenic diseases with enormous unmet medical need, and we're excited to now advance this innovative investigational medicine to the clinic. Our Phase 1 study aims to obtain data on safety and tolerability in addition to potential clinical activity in ASHE subjects and AIP patients with recurrent attacks," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer of Alnylam. "We're encouraged by the potential for ALN-AS1 to make a difference in the lives of people afflicted with acute hepatic porphyrias. In pre-clinical studies performed in rodent models of AIP, we have shown that subcutaneous administration of ALN-AS1 results in complete suppression of the toxic heme biosynthesis intermediates that cause disease symptoms and pathology. We very much look forward to the advancement of ALN-AS1 in the clinic and expect to share initial data from the Phase 1 trial in early 2016."
"Patients with AIP often present with acute, and at times recurrent attacks that are characterized by severe abdominal pain, neuropathy, neuropsychiatric manifestations, and, in very severe cases, paralysis and respiratory failure. Novel therapies are needed for porphyria patients who suffer from recurrent attacks. These patients can spend a significant number of days in the hospital every month and have a very poor quality of life," said Eliane Sardh, M.D., Ph.D., Senior Physician at the Porphyria Centre Sweden and the Centre for Inherited Metabolic Diseases and Department of Endocrinology, Metabolism and Diabetes at Karolinska University Hospital in Stockholm, Sweden. "I am encouraged with the pre-clinical data to date with ALN-AS1, which I believe support the potential for an RNAi therapeutic as a novel therapeutic option for patients with AIP and other acute hepatic porphyrias."
ALN-AS1 is a subcutaneously administered, investigational RNAi therapeutic that employs Alnylam's ESC-GalNAc delivery technology. ESC-GalNAc-siRNA conjugates are designed to achieve targeted delivery of RNAi therapeutic to hepatocytes through uptake by the asialoglycoprotein receptor, and enable subcutaneous dosing with increased potency and durability and a wide therapeutic index. In pre-clinical studies, multi-dose administration of ALN-AS1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS1 mRNA in the liver of non-human primates, with an ED50 of approximately 1.25 mg/kg. Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced production of ALA and PBG, the toxic heme intermediates in AIP. Pre-clinical studies with RNAi therapeutics targeting ALAS1 have been published by Alnylam and collaborators previously (Yasuda et al., Proc Natl Acad Sci USA 2014;111(21):7777-7782).
As per the filed CTA, the Phase 1 trial of ALN-AS1 will be conducted in three parts. Parts A and B will be randomized (3:1, drug:placebo), single-blind, single-dose (Part A) and multi-dose (Part B), dose-escalation studies, designed to enroll up to a total of 40 ASHE subjects. The primary objective of Part A and Part B is to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-AS1. Secondary objectives include evaluation of clinical activity for ALN-AS1 as measured by reduction in plasma and urinary levels of ALA and PBG. Part C will be an open-label, multi-dose study in up to eight AIP patients who experience recurrent porphyria attacks, and will assess safety, tolerability, PK/PD, and clinical activity of multiple doses of ALN-AS1. In addition, this part of the study will include an exploratory evaluation of the effects of ALN-AS1 on the number and severity of attacks and other disease symptoms, use of hematin and pain medications, number and duration of hospitalizations, and quality of life.
"Patients afflicted with acute hepatic porphyrias, such as AIP, can suffer from severe and recurrent attacks that are potentially life-threatening and that can result in a markedly decreased ability to lead a normal functioning life. Current treatment options are limited, especially for patients with recurrent attacks that often require monthly hospitalizations for administration of hematin and pain management," said Desiree Lyon, Co-Founder and Executive Director of the American Porphyria Foundation. "Today is an important step forward for our patient community, as ALN-AS1, a promising investigational medicine for the treatment of acute hepatic porphyrias, has entered clinical testing. I am so pleased with Alnylam's commitment to make a difference in the lives of our patients."
In addition to the Phase 1 trial, Alnylam and clinicians from the American Porphyria Consortium and The European Porphyria Network are currently enrolling patients in the EXPLORE trial, a prospective observational study of patients with acute hepatic porphyrias - including AIP, variegate porphyria, and hereditary coproporphyria - suffering from recurrent attacks. With this study, Alnylam and clinical investigators aim to learn more about the clinical course, management, and disease burden of patients with acute hepatic porphyrias that suffer from recurrent attacks.
In January 2014, Alnylam and Genzyme, a Sanofi company, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. Alnylam retains product rights inNorth America and Western Europe, while Genzyme obtained the right to access certain programs in Alnylam's current and future Genetic Medicines pipeline, including ALN-AS1, in the rest of the world. In certain defined instances, Genzyme has co-development/co-commercialization and/or global product rights. Genzyme's rights are structured as an opt-in that is triggered upon achievement of human proof-of-principle.
About ALN-AS1
Alnylam is developing ALN-AS1, a subcutaneously administered, investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias, including acute intermittent porphyria (AIP). AIP is an ultra-rare autosomal dominant disease caused by loss of function mutations in porphobilinogen deaminase (PBGD), an enzyme in the heme biosynthesis pathway that can result in accumulation of toxic heme intermediates, including aminolevulinic acid (ALA) and porphobilinogen (PBG). Patients with AIP can suffer from acute and/or recurrent life-threatening attacks characterized by severe abdominal pain, neuropathy (affecting the central, peripheral or autonomic nervous system), and neuropsychiatric manifestations. ALN-AS1 is an ESC-GalNAc-siRNA conjugate targeting ALAS1, a liver-expressed, rate-limiting enzyme upstream of PBGD in the heme biosynthesis pathway. Inhibition of ALAS1 is known to reduce the accumulation of heme intermediates that cause the clinical manifestations of AIP. ALN-AS1 has the potential to be a prophylactic approach for the prevention of recurrent attacks, as well as for the treatment of acute porphyria attacks.
About Acute Hepatic Porphyrias
The porphyrias are a family of rare metabolic disorders with autosomal dominant inheritance predominately caused by a genetic mutation in one of the eight enzymes responsible for heme biosynthesis. Acute hepatic porphyrias constitute a subset where the enzyme deficiency occurs within the liver, and includes acute intermittent porphyria (AIP), hereditary coproporphyria, and variegate porphyria. Exposure of acute hepatic porphyria patients to certain drugs, dieting, or hormonal changes can trigger strong induction of aminolevulinic acid synthase 1 (ALAS1), another enzyme in the heme biosynthesis pathway, which can lead to accumulation of heme intermediates that precipitate disease symptoms. Patients with one of the acute hepatic porphyrias can suffer from a range of symptoms that, depending on the specific type, can include acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, cutaneous lesions and possibly death if untreated or if there are delays in treatment. The only approved treatment for acute attacks is hematin (Panhematin or Normosang), a preparation of heme derived from human blood. Hematin requires administration through a large vein or a central intravenous line and is associated with a number of complications including thrombophlebitis or coagulation abnormalities. While hematin is not approved for prophylactic use (i.e., the prevention of acute attacks), it is often used in this manner in patients who experience recurrent attacks. Chronic administration of hematin has been found to result in renal insufficiency, iron overload, systemic infections (due to the requirement for central venous access) and, in some instances, tachyphylaxis.
About RNAi
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines. Alnylam's pipeline of investigational RNAi therapeutics is focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline of RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in cardiovascular and metabolic diseases; and Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that address the major global health challenges of hepatic infectious diseases. In early 2015, Alnylam launched its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics as a whole new class of innovative medicines. Specifically, by the end of 2020, Alnylam expects to achieve a company profile with 3 marketed products, 10 RNAi therapeutic clinical programs - including 4 in late stages of development - across its 3 STArs. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information about Alnylam's pipeline of investigational RNAi therapeutics, please visit www.alnylam.com.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-AS1 for the treatment of acute hepatic porphyrias, its expectations regarding the reporting of data from its ALN-AS1 clinical studies, its expectations regarding the potential market opportunity for ALN-AS1, its expectations regarding its STAr pipeline growth strategy, and its plans regarding commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage operating expenses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation to update any forward-looking statements.
"Remember.Research is the key to your cure!"
What is Variegate Porphyria?
Monday - June 22, 2015 @ 10:30:01
What is VP?
Variegate Porphyria (VP)
This form of hepatic Porphyria is most common in South Africans of Dutch ancestry. It is relatively uncommon elsewhere. It is an autosomal dominant disorder and may produce acute attacks (as in AIP) as well as chronic skin photosensitivity. The deficient enzyme is protoporphyrinogen oxidase. In acute attacks, urine PBG is increased as in AIP. Diagnosis of latent carriers is made by finding excess coproporphyrin in urine and both coproporphyrin and protoporphyrin in feces, or by DNA mutation analysis (see AIP). The most sensitive screening test for VP is probably a plasma porphyrin assay. In patients with skin manifestations, it is important to distinguish VP or HCP from PCT, because treatment by phlebotomy or low-dose chloroquine is ineffective in VP and HCP. Acute attacks are managed and may be prevented as in AIP.
To learn more please visit porphyriafoundation.org or call 1-866-APF-3635 for a comprehensive Dr. Kit or Patient kit sent out to you.
"Remember.Research is the key to your cure!"
Tony Mc Laughlins fight with VP from the UK
Wednesday - June 17, 2015 @ 10:30:00
Hi my name is Tony McLaughlin I'm 52 and from Yorkshire in the UK but now live in Galway Ireland.
I was diagnosed in 1993 with VP, after my sister found out she had VP, my sister went to see a cardiologist on an unrelated matter and the cardiologist recognized the skin symptoms which given it's rarity was a lucky break and they tested the rest of the family.
I have 2 grown daughters one was also diagnosed through genetic testing as having VP but she's 24 with no symptoms, although she has to be careful with unsafe drugs and the sun.
Since 1993 I was relatively stable apart from fragile skin in the summer, that was until 2010 when I had a severe attack exacerbated by dithering doctors who didn't believe all my symptoms were due to Porphyria and kept treating me for other things until my wife stepped in and read them the riot act, they quickly changed their tune and handed me over to a different team who got the Heam Arginate for the UK (in USA Panhematin) and saved my life, but because of the delay I'd developed all sorts of symptoms that took time to sort themselves out.
Since then I've had 5 more attacks but I recognize the symptoms early got myself to the hospital and have been treated with Heam every time.
All of my attacks have been caused by pain from other conditions notably Kidney stones and back pain, hopefully if we can stop the triggers we can stop provoking my attacks.
Mrs. Ludlow was an attractive woman in her mid-thirties, but she looked as if she could use a good nights sleep. Her nine-year-old daughter sat at her side. After introducing myself, I led them into my office and asked Mrs. Ludlow if she knew why she needed to see me. Well, to tell you the truth, no, she said, sighing. Were here because the Committee on Special Education at our elementary school said they need a report from you.
Why is your daughter being evaluated?
Nicoles a bright kid, but shes missed so much school this year that shes failing third grade. Theyre trying to decide whether to give her home tutoring, put her in special ed, or make her repeat the year. So they want to find out why she has these attacks. But frankly, Nicoles already been seen by more than a dozen specialists. So far, no ones been able to tell me whats wrong with her.
While Mrs. Ludlow spoke, her daughter sat stone still on a chair across from her, staring into space.
Well, Im a medical geneticist, I explained. I take care of children with birth defects and inherited diseases. Is there any reason to think Nicoles condition is inherited?
Not that I know of.
Well, if its all right with you, Ill begin by asking some questions about Nicoles past; then Ill examine her. Then well talk about where we go from there. Okay?
She nodded her head.
Lets start at the beginning, I said. How much did Nicole weigh at birth? As the words were coming out of my mouth, the child began to make a strange mewing noise. It sounded like a cat stuck in a closet. The noise came from somewhere deep inside the girls throat, not her vocal cords exactly but from somewhere farther down. After finishing my question, I gazed at Nicole, trying to figure out what she was trying to say.
Quiet, the girls mother said. Dont make that noise. Thats a bad noise.
Nicole, still staring off into space, immediately became quiet.
Shes usually a nice, sweet kid, said Mrs. Ludlow apologetically. But shes having one of her attacks. The attacks are the problem.
I stared at the little girl, trying to get her attention. Although she looked fine, she behaved as if she were in a world of her own. Never did she make eye contact with me; not once did she even look my way.
Has anyone suggested that Nicole might be autistic? I asked.
No. Shes usually very outgoing. Its only during her attacks that she acts this way. Can autism come and go like this?
I shook my head. To say this girl had grabbed my attention was an understatement. How often does this happen?
A couple times a year. Actually, its good youre seeing her today, so you can understand what Im talking about. When shes her normal self and I try to explain whats wrong with her, people usually think Im crazy.
How long does this last? I asked, though I wasnt sure what this actually referred to.
Cant be sure, the mother replied. Sometimes its just a day or two. The longest has been nearly four weeks. And nothing seems to bring them on. They just seem to come and go.
Are they seizures? I asked.
Thats what the neurologists have always thought. Over the years, Nicoles been seen by five neurologists. Shes been hospitalized three times for overnight brain-wave tests. Shes had two CT scans, an MRI, and about a hundred blood tests. Every test has turned out perfectly fine. Every doctor has told me that he could find nothing wrong with my daughter. Some have even accused me of making the whole thing up. But look at her-- you can verify Im not making this up, cant you?
I said yes, Id certainly be willing to swear in a court of law that she hadnt invented Nicoles illness. You seem to know a lot about medicine, I commented. Do you have a medical background?
No, she replied. But what Ive gone through with this kid has been a medical education.
Has anyone tried to treat these episodes with medication?
Sure, she responded without hesitation. Every neurologist has started Nicole on some form of antiseizure medication. Just last week the doctor we saw put her on Tegretol. None has done a bit of good. Some, if you ask me, have actually made her worse.
How old was Nicole when the episodes started? I asked, still groping in the dark.
As Mrs. Ludlow told her daughters story, the look of exhaustion lifted from her face. She explained that Nicole had been perfectly healthy until she was three and had surgery on an elbow shed fractured in a fall. But after the operation, she just never woke up from the anesthesia. It was terrifying--she went into a coma and nobody could bring her out of it. At first they thought shed suffered brain damage. They did a CT scan, but it was normal. They gave her all kinds of medications, antibiotics, steroids, but Nicole just wouldnt wake up. I was sure she was going to die.
I thought for a minute, trying to understand the relationship between the anesthesia and the onset of the illness. In the back of my mind, a distant bell began to ring. The story was starting to remind me of something. How long did she stay like that?
Two weeks. For two weeks I sat at her bedside, holding her hand, talking to her, trying to wake her up. The doctors kept telling me they couldnt find anything wrong. Then one day she just woke up. She opened her eyes, looked at me and said, Hi, Mommy, and that was it.
While her mother was talking, Nicole got up and walked over to my filing cabinet. She placed her face against the cabinets metal front and stood there, as rigid as a statue. Is she okay?
Mrs. Ludlow shrugged. I guess so. As all right as she ever gets during one of her attacks.
So after that first episode, was she back to her old self?
It was as if nothing had happened, she said, except that the right side of her face drooped. The neurologist told me she had facial palsy and that she might have it for the rest of her life. Of course, he was wrong--the doctors have been wrong about everything about Nicole. The droopiness lasted about a week. But since then its come back a few times, usually during or right after an attack.
On the pad on my desk, I wrote Coma after anesthesia and beneath it Recurrent facial palsy. The bell inside my head was ringing louder now. So how many of these attacks has Nicole had?
Mrs. Ludlow paused and sighed. Somewhere between 20 and 25.
Other than the coma and the facial palsy, I continued, what other problems have occurred during the episodes?
Lets see, Mrs. Ludlow said. Sometimes her speech gets slurred, as if shes had a stroke. The bell in my head was ringing even louder now. I wrote the words Slurring of speech on the pad. And insomnia, she added. Thats the worst part. Nicole can go four or five days in a row without sleeping. And of course I have to stay awake, too, because Im afraid she might hurt herself.
I wrote Insomnia on the next line of the pad. Undoubtedly this was the cause of Mrs. Ludlows haggard appearance. Anything else?
Yes, she gets bad pains in her neck, her chest, and her belly. Once I thought she was having a heart attack. Another time the doctors in the emergency room wanted to take her appendix out.
As I wrote Pain on the pad, I thought I finally knew what was wrong with Nicole. I just needed one more bit of information to confirm my suspicion. During these attacks, is there anything unusual about Nicoles urine?
Youre the first person ever to ask, but there is something. When shes sick, Nicoles urine gets very dark. Does that mean anything?
It sure did. By now the bells in my head were sounding an alarm. I was almost positive that Nicole had a disorder called acute intermittent porphyria, or AIP.
Much as I hate to admit it, my flash of diagnostic insight wasnt the result of my being smarter than the dozen other doctors whod seen Nicole. I hadnt read more articles, I didnt have better clinical acumen, and I hadnt asked more-probing questions. The explanation for my medical epiphany was simple.
In the weeks prior to the Ludlows visit, I was at work on a book about historical figures who were afflicted with genetic diseases. Just the month before, Id finished a chapter on King George III, the English monarch at the time of the American Revolution. Throughout his reign, King George suffered a series of mysterious--and ultimately incapacitating-- illnesses. Just like Nicoles, his attacks came and went without warning. His symptoms--nervous trembling, altered consciousness, intractable pain, and terrible insomnia--mystified doctors. In 1966 two British psychiatrists finally proposed a logical explanation for King Georges ailment. Based on a study of the records kept by the kings personal physician, they suspected that King George had probably suffered from porphyria.
The porphyrias are a group of rare inherited disorders that affect the bodys ability to make hemoglobin, the molecule that enables red blood cells to absorb and release oxygen. Heme is the iron-containing portion of hemoglobin, and patients with porphyria dont make one of the several enzymes needed to make normal amounts of it. As a result, many patients with porphyria have two symptoms in common. First, they are anemic because they cannot make enough heme. Second, because heme is not being assembled properly, the precursors of heme build up in the blood. The accumulation of these chemicals, which are toxic to the skin, the liver, and the nervous system, can cause an array of other puzzling symptoms.
The form of porphyria that affected George III, however, does not cause constant symptoms. Under normal circumstances, there is enough enzyme to maintain good health. But during illness or emotional stress, or following exposure to certain drugs or chemicals, patients can experience unexplained aches and bizarre neurological disturbances. And because of the buildup of heme precursors, they excrete abnormally dark urine.
Nicoles first attack had followed exposure to anesthetic agents, some of which are known to exacerbate symptoms. In the following years, she had been treated with the anticonvulsant phenobarbital, which also makes symptoms worse. In fact, the attack that was at that moment gripping Nicole may well have been brought on by treatment with the anticonvulsant drug shed begun to take the week before.
The more I thought about it, the more convinced I became that Nicole had AIP. Although the condition rarely causes symptoms in young children, the resemblance between her symptoms and King Georges was too striking for mere coincidence. To prove the diagnosis, though, I had to complete two tasks. First, since AIP is inherited when a gene is passed from an affected parent to a child, I had to find out which of Nicoles parents also suffered from the disease. And second, I had to prove that Nicoles blood bore evidence of the biochemical abnormality that causes AIP. I turned my attention to the first of these tasks.
I told Mrs. Ludlow that Nicoles dark urine might be significant and continued with my questioning. How was your pregnancy with Nicole?
Awful, Mrs. Ludlow replied. I was hospitalized twice. The first time, I was in my sixth week. I began having terrible belly pain. My doctor operated to see what was going on.
Did he find anything wrong?
No, thats the strange part: everything was fine. Then about a week later, the pain just went away. Weird.
I was ready to burst. Mrs. Ludlows unexplained pain was most likely an attack of porphyria. I kept probing. When was the second hospitalization?
A month later. It was terrible. I was vomiting so much I was hospitalized for six weeks for dehydration.
Again, these symptoms were consistent with porphyria. The stress of pregnancy could have triggered the attacks. Have you ever had any episodes like Nicoles? I asked. Mrs. Ludlow shook her head.
When I asked about the rest of the family, Mrs. Ludlow said that her husband and his family were in excellent health, but members of her side of the family had had a series of unexplained health problems. My mothers okay, she said, but my fathers a mess. People think hes a drunk because he has blackouts, but I know he never takes a drink--it makes him sick to his stomach. And then, his older sister has had seizures all her life..
Anything besides seizures? I asked.
She shook her head. That sister has a daughter whos okay
That would be your first cousin?
Yes, shes okay, but her daughter has some rare disease. I dont know what its called.
Porphyria? I asked, nearly jumping out of my skin.
Mrs. Ludlows eyes opened wide. Yes, thats it. How did you know?
Mrs. Ludlow, Ive been thinking for the past few minutes that porphyria would explain all of Nicoles problems. Since its an inherited condition, Ive been waiting for you to tell me that someone else in your family has it.
She seemed mystified. But how can my cousin and I both have daughters with it if nobody else in the family has it? she asked dubiously.
Well, Nicole and your cousins daughter arent the only ones who have it. Im pretty sure those problems you had during your pregnancy were episodes of porphyria. And your fathers blackouts and his inability to tolerate alcohol? Those are probably also caused by porphyria.
What about my cousin? Mrs. Ludlow asked. Shes never been sick
Thats whats strange about this disease, I interrupted. It varies widely from one person to the next. Some people are sick all the time, others never have a sick day in their lives. I cant explain it better than that.
Mrs. Ludlow considered this. If she really does have porphyria, and Im not sure she does, what can we do?
Well, we cant cure it, but we can do a lot to help her. I explained that putting Nicole on a high-carbohydrate diet and keeping her off certain medications could prevent the attacks. The first step would be to take Nicole off Tegretol. I also explained that I needed samples of blood and urine from Nicole to confirm the diagnosis. I then asked if Mrs. Ludlow had any more questions.
Just one, she said. How were you able to make this diagnosis when so many other doctors didnt think of it?
I just shrugged. What I should have told her was that we doctors are just like everyone else. We go to the movies, watch TV, read newspapers and novels. If we happen to see a patient who has symptoms of a rare disease that was featured on the previous nights Movie of the Week, were more likely to consider that condition when making a diagnosis.
Blood tests ultimately confirmed my diagnosis of acute intermittent porphyria in Nicole Ludlow and her mother. But I didnt make the diagnosis because Im a brilliant diagnostician or because Im a sensitive listener. Had I seen Nicole one year before, Im sure I would have failed. No, I succeeded where others failed simply because the Ludlows and I managed to run into each other in exactly the right place, at exactly the right time.
"Remember.Research is the key to your cure!"
The story of Kristen Elizabeth Harris and Porphyria
Friday - June 12, 2015 @ 10:30:00
My name is Kristen. I have been diagnosed of Porphyria since I was 7 years old. This is now 11 years ago roughly. The doctors did not know what was wrong with me. They were doing ever imaginable test and kept referring me and my mother back out to so many other different specialists. The tests were coming back negative for everything and eventually the did not even believe my mother anymore and assume she was making everything up. There was a doctor in the Bronx, New York, Doctor Robert Marion at Montefiore Hospital. He was a new doctor and just studied the signs of Porphyria. After questioning my mother on the medications I was on and my symptoms he realized what I did have. My mother knew that there was some weird rare disease that her father and others in her family had but, could not remember it. Finally after Doctor Marion asked questions and said the name she confirmed that is what our family had and my grandfather died of. I started associating with the American Porphyria Foundation in 2003 at the age of 16. Thanks to Desiree Lyon and Yvette Strange I have been able to fight this. I still go through my trials and have to go in and out of the hospital for treatments. "The American Porphyria Foundation has guided my emergency room doctors on how to properly care for me not just emergency room, but also in accordance to what I believe in religiously with my conscience." There is a song by Melissa Etheridge called I run for life. There is a verse says, "And they cut into my skin and they cut into my body but they will never get a piece of my sole." No matter what the doctors do I will always have my sole and my faith in Jehovah God no matter what this disorder brings. This is my story of Porphyria. Stay tuned for the next blog from Discovery magazine on the Girl who Mewed! "Remember.Research is the key to your cure!"
NBC June 14th on EPP- Explanation from APF
Wednesday - June 10, 2015 @ 10:30:01
Please be Sure to check out " Out of the Shadows" experiences of people who have EPP. The date it will air is Sunday June 14th 2015. Please check your local NBC stations for times.
You may ask though what exactly is EPP Porphyria? Please feel free to read more about this explanation this information comes directly from the APF.
Erythropoietic Protoporphyria (EPP) or Protoporphyria
Erythropoietic Protoporphyria (EPP) or Protoporphyria
Erythropoietic Protoporphyria is characterized by abnormally elevated levels of protoporphyrin IX in erythrocytes (red blood cells) and plasma (the fluid portion of circulating blood), and by sensitivity to visible light that is usually noticed in early childhood and occurs throughout life. EPP can result either from mutations of the ferrochelatase gene (FECH), or less commonly the delta-aminolevulinic acid synthase-2 gene (ALAS2). When EPP is due to an ALAS2 mutation it is termed X-linked protoporphyria (XLP), because that gene is found on the X chromosome.
Protoporphyrin accumulates first in the bone marrow in EPP, and then in red blood cells, plasma and sometimes the liver. Protoporphyrin is excreted by the liver into the bile, after which it enters the intestine and is excreted in the feces. It is not soluble in water, so is not excreted in the urine.
EPP is the third most common type of porphyria, and the most common in childhood. It causes very painful photosensitivity and can greatly impair quality of life. Delay in diagnosis is greater than with any other type of porphyria.
Swelling, burning, itching, and redness of the skin may appear during or after exposure to sunlight, including sunlight that passes through window glass. This can cause mild to severe burning pain on sun-exposed areas of the skin. Usually, these symptoms subside in 12 to 24 hours and heal without significant scarring. Blistering and scarring are characteristic of other types of cutaneous porphyria but are unusual in EPP. Skin manifestations generally begin early childhood and are more severe in the summer.
There is an increased risk of gallstones, which contain protoporphyrin. Excess protoporphyrin can also cause liver damage. Less than 5% of EPP patients severe liver damage and a condition caused protoporphyric hepatopathy that sometimes requires liver transplantation.
Diagnosis and Genetic Counseling
EPP should be suspected in anyone with non-blistering photosensitivity especially when is it prolonged and beginning in childhood. It is easy to make a diagnosis, or rule it out, once it is suspected.
The diagnosis of EPP is established by finding an abnormally high level of total erythrocyte protoporphyrin, and showing that this increase is mostly free protoporphyrin rather than zinc protoporphyrin. There is considerable confusion about which test to order. Sometimes laboratories have measured only zinc protoporphyrin and reported results incorrectly as protoporphyrin or free erythrocyte protoporphyrin (FEP). Laboratories that measure total erythrocyte protoporphyrin, free protoporphyrin and zinc protoporphyrin and report results reliably are:
Porphyria Laboratory and Center, University of Texas Medical Branch at Galveston, 1-409-772-4661
Mayo Medical Laboratories, 1-800-533-1710
ARUP Laboratories
Porphyrins are almost always elevated in plasma in EPP, but may be normal in mild cases. Fecal porphyrins may be normal or increased.
An experienced biochemical laboratory can usually distinguish between patients with EPP and XLP, because the former have much less zinc protoporphyrin in their erythrocytes. This can be explained because in the marrow the enzyme ferrochelatase not only normally makes heme (iron protoporphyrin) from protoporphyrin and iron, but can also make zinc protoporphyrin, especially when excess protoporphyrin is present or iron is deficient. However, this does not replace DNA studies.
Rarely, EPP develops in adults in the presence of a bone marrow disorder such as polycythemia vera, and is due to expansion of a clone of red blood cell precursors in the marrow that is deficient in ferrochelase.
DNA studies are important for confirming the diagnosis of EPP and XLP and for genetic counseling. This should be completed first in a person known to have the disease, and the information about the mutations in that individual used to guide testing of family members.
When EPP is due to a FECH mutation the inheritance is described as autosomal recessive. It is most common to find that one severe mutation is inherited from one parent and another weak mutation inherited from the other parent. The weak mutation is quite common in normal Caucasians, rare in Blacks and even more common in Japanese and Chinese populations. This mutation is sometime referred to as hypomorphic because it results in formation of a less than normal amount of ferrochelatase. But is does not cause EPP unless it is paired with a severe mutation. The severe mutation is characteristic for an EPP family and is present in all affected individuals. Carriers of the severe mutation are not affected because they do not have the weak mutation. Affected individuals and unaffected carriers can transmit the severe mutation to the next generation. Some of their children will have EPP if the other parent has a copy of the weak mutation. Rarely, the weak mutation is absent in an EPP family and two severe mutations are found, with at least one producing some ferrochelatase.
In XLP, mutations of the ALAS2 gene, which is found on the X chromosome, causes an increase in the production of the enzyme ALAS2 in the bone marrow. Several of these gain of function mutations have been described in different XLP families. In XLP protoporphyrin production exceeds that needed for heme and hemoglobin formation. Like hemophilia and other X linked genetic diseases, XLP is more common in men. Women have two X chromosomes and are usually not affected because they have a normal as well as a mutated ALAS2 gene. Men have only one X chromosome and will be affected if they inherit an ALAS2 mutation. Women with an ALAS2mutation will, on average, pass that mutation to half of their daughters (who will usually be unaffected carriers) and to half of their sons (who will be affected).
Treatment and Management
1. Sunlight protection
Protection from sunlight is the mainstay of management of EPP, and this is necessary throughout life. Disease severity and porphyrin levels in erythrocytes and plasma probably remain high and relatively constant throughout life in EPP. However, this has been little studied and more longitudinal observations are needed. Life style, employment, travel and recreation require adjustment in order to avoid painful reactions to sunlight and even from exposure to fluorescent lighting. For these reasons EPP can substantially affect quality of life.
Protective clothing, including broad-brimmed hats, long sleeves, gloves and trousers (rather than shorts), is beneficial. Several manufacturers specialize on clothing made of closely woven fabrics for people with photosensitivity.
2. Beta-Carotene (Lumitene Tishcon)
Beta-carotene is an over the counter product that was originally developed in a purified form as a drug for the treatment of EPP, and was shown to be effective by Dr. Micheline Mathews-Roth at Harvard University and others. The pharmaceutical grade formulation is now distributed by Tishcon as Lumitene, and can be ordered by calling 1-800-866-0978 or via the website www.epic4health.com. Other products are less standardized and reliable and are not recommended.
Beta-carotene provides protection by quenching reactive oxygen products that form when protoporphyrin is activated in the skin by light. It is important to take an amount that is adequate to be protective. For more information about Lumitene, including a recommended dosing schedule, please see the Lumitene section of this website.
3. Other considerations
In an occasional patient, protoporphyrin causes liver problems, so monitoring liver function is important. EPP patients should also not use any drug or anesthetic which causes cholestasis (slowing down bile flow), and should also avoid alcohol. Women should avoid medications containing estrogen (birth-control pills, hormone replacement therapy), and men should avoid testosterone supplements, as these substances can also have deleterious effects on the liver of a person with EPP.
Consult a specialist. Because EPP is a rare condition, most physicians are not knowledgeable about it. Contact The American Porphyria Foundation, 713-266-9617 for contact with an expert and to provide further information. A Medic Alert bracelet with instructions to contact a specialist if needed is a worthwhile precaution.
Yearly monitoring. Testing to include erythrocyte total protoporphyrin, plasma porphyrin, complete blood counts, ferritin and liver function tests should be done yearly. Porphyry levels are expected to be stable and liver tests to remain normal. EPP patients may have evidence of iron deficiency, and an iron supplement may be advisable if the serum ferritin is below about 20 ng/mL.
Vitamin D. Because they avoid sunlight, EPP patients are likely to be deficient in vitamin D. A vitamin D supplement with calcium is recommended for bone health.
Liver protection. It is important to avoid other causes of liver disease that might promote the development of liver complications from EPP. Patients should avoid alcohol and other substances that might damage the liver, including many herbal preparations, and be vaccinated for hepatitis A and B.
Surgical lights. Strong operating room lights can cause photosensitivity of the skin and even surfaces of internal organs. Flexible membrane filters, such as CL5-200-X from Madico Co., are available to cover surgical lights and offer some protection. This is especially important in EPP patients with liver failure, which causes even greater increases in protoporphyrin levels and photosensitivity.
Drugs. Drugs that are harmful in other porphyrias are not known to make EPP worse, but are best avoided as a precaution. This may include estrogens and other drugs that might reduce bile formation. A short course of a non-steroidal anti-inflammatory drug can provide some pain relief after an episode of photosensitivity, but can cause ulcerations of the digestive track especially with prolonged use.
Laser treatment. According to Dr. Roth, laser treatments for hair removal or eye surgery have not been a problem in EPP people. But the doctor should be made aware of the diagnosis, and that laser output between 400 and 650 nanometers might be harmful. Before hair removal treatment, the doctor may irradiate a small area of the skin to be treated for the length of time it will take to do the hair removal to ascertain if the patient would react within the period of time that a reaction to sunlight would be expected in that patient.
Children with EPP. Avoiding sunlight can be difficult for children with EPP who have less sunlight tolerance than their friends. Camp Discovery is an option for such children. It provides a week-long summer camping experience of fishing, boating, swimming, water skiing, arts and crafts, and just plain fun for young people with skin disorders, and is sponsored by the American Academy of Dermatology. Full scholarships, including transportation, are provided by the American Academy of Dermatology through generous donations of their members and other organizations. Members of the Academy are asked to recommend candidates for Camp Discovery, so ask your child's doctor about sending your child to Camp Discovery.
Disneyland and Disney World are responsive to people with sun sensitivity. They will provide a pass to enable you to enter attractions without waiting in line in the sun.
Disneyland Go to "Town Hall" and explain your problem with photosensitivity. You should bring a physician's letter with you as well as an APF brochure explaining the type of Porphyria you have. The staff will ask you some questions about your limitations (e.g., whether or not you can climb stairs) and how many are in your group. Next time you return, be sure to bring the old card with you, as it will only take about half as long to go through the process on your next trip.
Disney World Proceed to the "Guest Relations" office at any park (Magic Kingdom, EPCOT, etc.) and request the Special Assistance Pass.
Remember to bring a doctor's note and explanation of your condition, because it is not necessarily visible. People on duty may not be familiar with light sensitivity and its consequences.
Research Opportunities
Patients with EPP and XLP can participate in the research through the Porphyrias Consortium. The American Porphyria Foundation has information on what research protocols are currently open.
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The Porphyrias Consortium is conducting a Longitudinal Study to better define the natural history of the disease. This study is currently open for enrollment of new patients.
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The Porphyrias Consortium will be starting a pilot study soon on a drug that may lower porphyrin levels in EPP.
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Clinuvel Pharmaceuticals is developing afamelanotide (Scenesse) for the treatment of EPP. This drug is given by injection and increases skin pigmentation. Another study of this drug is expected to open within the next year.
All patients with porphyria are encouraged to enter the Porphyrias Registry at the Porphyrias Consortium website. A link to this website is found on the website of the American Porphyria Foundation. Registration demonstrates to NIH that patients and their families think that research on porphyrias is important. You can also ask that one of the 6 porphyria center in the Consortium contact you.
"Remember.Research is the key to your cure!"
Natalia Nikova Summer Vacation and AIP
Monday - June 8, 2015 @ 17:06:08
It's summer time have you taken a vacation yet? Please read the reminders off a new personal experience from Natalia Nikova
Acute Intermittent Porphyria
Beware of Mountains
My name is Natalia Nikova. I was born in Russia in St. Petersburg. I have AIP.
I went through horrible surgeries and sufferings in Russia before I was properly diagnosed. That happened when I was between 25 and 30 years old.
After that I was receiving capsules of Adenil through the Red Cross for about four years and injecting myself two times a day. My recovery was very slow but at the age of 39 I started to feel better and I was able to immigrate to the USA with my daughter and my mother.
I managed to change my profession from Choral conductor to a computer programmer to support my family and my porphyria's symptoms almost disappeared. Now I am 63 years old and in August 2004 all of a sudden I had a reminder. I and my husband went to Peru. I got immediately sick in Cusco from the high altitude but the altitude sickness was greatly aggravated by porphyria. In addition to a headache and shortness of breath I had nausea, high fever, high blood pressure and grazing pain in my stomach. In fact I became so sick that we had to change our entire itinerary and move to lower regions in Peru. That was not too much fun because I am a bird watcher I was looking forward to go to Colca Canyon to see Andean Condor. Even after we returned from Peru I was sick for two weeks with general weakness.
I hope that sharing this story will help some people in planning their vacation.
"Remember.Research is the key to your cure!"
Longitudinal Study of the Porphyrias
Wednesday - June 3, 2015 @ 10:30:02
Longitudinal Study of the Porphyrias
We are looking for patients volunteers for the 7201 Longitudinal Study of the Porphyrias. Participants of this study DON'T have to travel to the research site. All that needed is to answer porphyria-related questionnaire over the phone. You will be working closely with porphyria experts and researchers.
The purpose of this long-term follow-up study is to provide a better understanding of the natural history of porphyrias, as affected by available therapies, and to aid in developing new forms of treatment.
Volunteering for research is the most important action you can take to change your future health because Research is the Key to Your Cure. You can be a Medical Hero and join many patients, who gave some of their time to help find important answers leading to new and improved treatments and a cure.
In order to participate in a study, please contact us at the APF 866-apf-3635.
"Remember.Research is the key to your cure!"
True Joy Poem
Thursday - May 28, 2015 @ 14:38:09
True Joy
I'll be happy once I've done this certain thing.
We all say this often not realizing what it brings.
We look only to the future for our happiness.
Letting life slip through our fingers in its fullness.
Will we really feel complete when the task is done,
or look back and see how we missed so much fun?
Self consumed so we can't see anything else,
hurting those we love as well as ourselves.
So many things around us to be grateful for,
when seeking for an answer willingly open the door.
So often, others see what's in front of our face,
but we're too blind to look as we're snared in the race.
What is this life supposed to be about?
Is it money, fortune, fame, or a big house?
When speaking to a man on his dying bed,
none of these answers are what he said.
Family, love, laughter are what we should seek.
These are the precious things right outside your door.
"Remember.Research is the key to your cure
The Illness of Vincent Van Gogh. Porphyria? From the Wilfred Niels Arnold Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KA, USA
Friday - May 22, 2015 @ 10:30:02
This Is Lengthy but a well read and documented case. A must read!
The Illness of Vincent van Gogh Wilfred Niels Arnold Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KA, USA ABSTRACT Vincent van Gogh (18531890) was a wonderfully accomplished artist whose work is now widely appreciated. He created a great number of masterpiece paintings and drawings in just one decade devoted to art. His productivity is even more remarkable when considered in the context of his debilitating illness. He suffered from medical crises that were devastating, but in the intervening periods he was both lucid and creative. He left a profound, soul-searching description of his jagged life in his correspondence, which provides the basis for the present analysis. An inherited metabolic disease, acute intermittent porphyria, accounts for all of the signs and symptoms of van Goghs underlying illness. On this 150th anniversary of the birth of Vincent van Gogh it is appropriate to revisit the subject and to analyze the lack of organized skepticism in the popular media about other diagnoses.
Vincent van Gogh was born in the presbytery of the Dutch Reformed Church of Zundert, in the southern region of The Netherlands, at 11:00 am on March 30, 1853. The obstetrician did not have far to run the office of Dr. Cornelis van Ginneken was right next door. There were no problems on that day. They would tumble out later. An eventful life was underway and it would last just thirty-seven years and four months. Today, van Gogh is on everybodys list of outstanding artists and in every catalog of creative people. He continues to find an appreciative audience of young and old, novice to connoisseur, all untrammeled by differences in cultural background or artistic education. It was not always so, at the time of his suicide in 1890 the accomplishments of Vincent were acknowledged by only a small cadre of friends and followers. No more than a handful of critics had put pen to paper. Formal recognition during his life was restricted to exchanges of paintings with other artists, gifts to friends and doctors, acceptance of canvases toward financial obligations, three sets of commissions, a drawing sold in The Hague, a few items sold in Paris, a selfportrait sold to a London dealer in 1888, and one sale from an influential Les Vingt exhibition (1890) in Brussels.1 He died still writing of hopes for future recognition, but indeed it was a deep disappointment for an artist who had been confident enough to follow the precedents of Michelangelo Buonarroti, Raphael Santi, and Journal of the History of the Neurosciences 2004, Vol. 13, No. 1, pp. 2243 Address correspondence to:Wilfred Niels Arnold, Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KA 66160-7421, USA. Tel.: þ1-913-588-7056. Fax: þ1-913-588-7440. E-mail: warnold@kumc.edu 1The sale of van Goghs artwork during his lifetime was obviously meager, but this list should replace the popular misunderstanding that Vincent sold only one painting. 10.1080/09647040490885475$16.00 # Taylor & Francis Ltd. Rembrandt van Rijn by using his first name alone for professional purposes.2 Posthumous praise for his creations roused attention but surely it has been the complementary interest in extraordinary aspects of the person, especially his underlying illness, that has made Vincent van Gogh a household name. His jagged life was marked by early years of uncertainty, interludes of luckless love affairs, wrenching episodes of self-mutilation, and crises of debilitating illness. Creative people who have shaken the world a bit are generally surrounded by popular contemplations about their physical and mental health. And in the visual arts the individual who makes the advance is all too often suspected of some individual abnormality, as if there were a need to invent an exotic explanation for the novelty. But in the case of van Gogh there were certainly enough unusual episodes to raise the question of mental derangement even during his lifetime. Given the extraordinary influence of the man on succeeding generations there are ample justifications for serious studies on whether medical problems affected his life or his artwork.3 THE PROBLEM Superficial interest and comment on van Goghs illness grew with every exhibition of his work. It became an industry with its own history. As a result, the typical newspaper article or exhibition essay declared that there were one hundred and one diagnoses on van Goghs illness!4 Six or seven examples were proffered, all embraced with equal weight by the reporter and without the benefit of a word of evaluation. Hopes of finding a better perspective in journal articles and books have not always been filled because the majority of the authors promoted pet ideas with selective inclusion of what they believed to be supporting data. I believe, axiomatically, that any reasonable working hypothesismust address all of the medical information; this includes family history and the artists lifestyle, as well as the underlying illness. The interaction between congenital disease and exacerbation factors is central to our argument. After Dr. Loretta Loftus and I published our working hypothesis of acute intermittent porphyria for Vincent and discussed the differential diagnosis (Loftus & Arnold, 1991) we were surprised to find that some critics, who did not offer any assessment of the facts we presented, were quick to respond with undocumented personal preferences in newspaper stories or letters-tothe- editor. Their epistles promoted alternatives that they claimed were more easily understood or more common disease entities, as if poor Vincent should become a poster-boy for the disease currently in vogue for creative people. Some made passing comparisons with other famous persons but usually without data on any of them. In some quarters the same weight was given to an opinion as to a well-referenced analysis. A large section of my subsequent book (Arnold, 1992) was devoted to van Goghs underlying illness. Therein I produced tables of Vincents own references (from his letters) organized by particular medical signs and symptoms, thus offering future scholars the benefit and convenience of a concordance. In the chapter Other Hypotheses I started with the assumption that all the authors were sincere but found that only a few advanced the field. It was also apparent tome that so many of those suggestions were loosely conceived and poorly documented, but they landed in the literature and in some cases had been widely quoted and requoted (errors to the third degree) without benefit of common sense. A blatant example is the silly claim of digitalis poisoning as a cause of van Goghs underlying illness. Art historians and others were quick to remark upon van Goghs occasional high yellow palette. This was hardly a revelation because the artist himself had written about his exaggerated use of yellow pigments and had coined the phrase. Vincents fondness for yellow can be gauged from his letters in the 18871890 period wherein he mentions the yellow of his surroundings more 2The paintings he signed (a small fraction of the total) were simply inscribed Vincent. I will use Vincent, van Gogh, and Vincent van Gogh interchangeably. 3Some commentators, mostly from the art history ranks, have denied the necessity to explore these questions. The possible reasons are analyzed later. 4I have encountered no more than a dozen serious proposals, but within each category there have been numerous renditions and rediscoveries. THE ILLNESS OF VINCENT VAN GOGH 23 than any other color (Arnold, 1992). But Lee (1981) was bold enough to propose that van Gogh suffered from a xanthopsia, wherein the patient has a reversible view of the world as if through a yellow filter, and that Vincent had been overexposed to digitalis, as a decoction of the foxglove plant. There is no doubt that too much digitalis will have this effect; the observation dates from the original dissertation (Withering, 1785); but there is no evidence that van Gogh ever took the drug, and artistic preference is still the best working hypothesis for the high yellow canvases (Arnold & Loftus, 1991). Also, and more important in the present context, it is absurd to include digitalis poisoning in lists of possibilities to explain all his neurologic and psychotic problems that culminated in suicide. The goal of the present review is fourfold: to evaluate our current understanding of van Goghs illness; to analyze some of the cultural and social aspects that impinge on (and interfere with) this field of van Gogh scholarship; to recommend a higher level of organized skepticism; and to promote the operational concept that the canons of proof associated with the hard sciences should also be applied to biography. THE IMPORTANCE OF THE LETTERS Theo van Gogh (18571891), who provided the emotional and financial supports for his brothers final decade, had realized the value of Vincents correspondence as a rich source of artistic and human interest. But he died the next year after Vincents suicide, and it took Theos widow, Johanna van Gogh-Bonger (18621925), another twenty-four years to decipher, translate, and arrange the letters before the first reasonable compilation appeared. In the preface, Johanna gave an additional reason, It would have been an injustice to Vincent to create interest in his personality ere the work to which he gave his life was recognized and appreciated as it deserved. (van Gogh-Bonger, 1978, xiii) The decision by Johanna van Gogh-Bonger to publish in English was based on her insightful anticipation of a world-wide audience for both Vincent the man and the huge amount of artwork that she inherited. She was well versed in the language and was also assisted in English phrasing and idiom by Helen Apel Johnson (Johnson, 1934). For many years the only edition of the letters that approached completeness was in English, and that had a profound effect upon the history of van Gogh scholarship. Vincents namesake nephew, V.W. van Gogh (18901978), identified as Vincent the Engineer, followed his mother in the activities of preserving the art work of his Uncle and organizing the copious correspondence, for which he anticipated the research potential by stating in his introduction that, the letters . . . are the only genuine source of details on his [Vincents] life (van Gogh, 1978, xi). During our 1990 conversation, Dr. Albert Lubin, professor of psychiatry and a van Gogh commentator (Lubin, 1972), made a special point about Vincents nephew being very much the amateur psychologist and a supporter of this type of enquiry. Unfortunately, in my opinion, Vincent the Engineer also endorsed some of the more mystical interpretations of the artists life.5 The three volumes of letters, memoirs, and editorial comments (van Gogh, 1978) are an important social, medical, cultural, and literary compilation. The descriptions of illness by the patient himself are central to our subject.6 In this review all references from The Complete Letters 5Dr. Humberto Nagera, another psychiatrist with direct contact, recently spoke to me about the Engineer being at odds with Paul-Louis Gachet (18731962), the son of Dr. Paul-Ferdinand Gachet (18281909). The father was Vincents last attending physician. Paul-Louis was a seventeen-year-old eyewitness commentator on Vincents final months in Auvers-sur-Oise, whereas the Engineer had to rely on information that was at best second-hand. One wonders whether the enmity of van Goghs nephew for young Gachet encouraged a splinter group that found fault with Dr. Gachets management of Vincents case and later criticized the whole Gachet family for exploitation of his art legacy. Their argument remains unconvincing and flies in the face of the generous donations (in 1949, 1951, and 1954) of van Gogh paintings to the state by Paul-Louis Gachet and his sister Marguerite (18691949). 6Most van Gogh commentators will not argue in public about the necessity of reading The Complete Letters, but it is no small undertaking (1,809 pages in all) and one may wonder how many have. 24 WILFRED NIELS ARNOLD will be noted, parenthetically, by letter numbers as they appear in the English edition of 1978. They overshadow the brief notes and register entries (Tralbaut, 1981) that have survived attending physicians in The Hague (unidentified hospital-doctors), Eindhoven (Dr. Van der Loo), Antwerp (Dr. Cavenaille), Paris (Drs. Rivet and Gruby), Arles (Drs. Rey and Urpar), St. Re´my (Dr. Peyron), and Auvers (Dr. Gachet). It seems inconceivable that Dr. Paul Gachet (18281909) kept no records, yet no journal or diary of patient visitations has been forthcoming from his office in the home at Auvers-sur-Oise.7 Biographical notes on all of the above physicians, as well as the influence of the home-remedies of Francois- Vincent Raspail (17941878), have been published (Arnold, 1992). MEDICAL SUMMARY Vincents ailment was characterized by episodes of acute mental derangement and disability which were separated by intervals of lucidity and creativity. Moreover, attending physicians, family, friends, and the artist himself were all surprised and encouraged by the rapidity of the recoveries after each crisis (van Gogh-Bonger, 1978). His serious illness developed late in the third decade, as evidenced by his concern with the possibility that [my] family might take steps to deprive me of the management of my affairs and put me under guardianship (letter 204). There was a family history of mental illness (Lubin, 1972; Tralbaut, 1981; Arnold, 1992). His underlying complaint was characterized by frequent gastrointestinal problems (letters 448, 530, B4, etc.), and at least one bout of constipation that required medical intervention (Tralbaut, 1981, pp. 177-8). The condition caused fits with hallucinations, both auditory and visual, (letters 592, W11, etc.) and evoked partial seizures (Tralbaut, 1981, p. 276). Periods of incapacitating depression and physical discomfort were severe and grave enough to provoke self-mutilation and eventual suicide (van Gogh-Bonger, 1978). Some of his bouts of sickness may have been associated with fever (letter 206) and sexual impotence (letter 506). His ailment was exacerbated by overwork (letter 173), malnutrition and fasting (letters 440, 571), environmental exposure (letter B15), excessive ingestion of alcoholic beverages (letter 581, etc.), especially absinthe (letter A16), and a proclivity for camphor and other terpenes (Arnold, 1988). The symptoms were palliated during institutionalization with better diet, alcohol restriction (letters 595, 599), and administration of bromide therapy (letter 574). In spite of their severity he did not experience any permanent, functional disability after any attack (Lubin, 1972; Tralbaut, 1981; Arnold, 1992). The reader is referred to Arnold (1992) for a much fuller treatment. In the paragraphs that follow I shall emphasize and explain specific aspects of van Goghs illness that are central to our working hypothesis and also dismissive of so many other hypotheses from the past. AGE OF ONSET In 1882, Vincent entered the city hospital at Brouwersgracht (a section of The Hague, in The Netherlands) with a gonorrheal infection, for an anticipated stay of no more than 14 days (letter 206). However, the hospital register (Tralbaut, 1981) indicated that Vincent was admitted June 7 and was not discharged until July 1 (a total of 25 days). To the surprise of his doctors, things took a turn for the worse after about 14 days, and Vincent complained by letter on June 22, of a dreadful weakness and wondered if there had been some complication that would make things worse (letter 208). He was moved to a new ward. The symptoms were only briefly described by Vincent but it extended his stay in the hospital for another 11 days. Was it a complication or a paroxysm? 7Son and daughter maintained the residence after the doctors death in 1909, and they were renowned for the care with which they preserved their fathers medical instruments and memorabilia. They had no children and were survived by distant relatives. Rumor has it that somewhere along the way all of Dr. Gachets records were intentionally destroyed to protect the privacy of his patients. His views survive only in the form of interesting anecdotes, and indirect reports with poor documentation of time or place. THE ILLNESS OF VINCENT VAN GOGH 25 There was a bizarre supplement. Van Gogh claimed that the attending physicians were willing to attest to his sanity (letter 206) if it were challenged again by his father. This statement is startling at first encounter but information taken from other letters indicates that his father had considered having him committed to an asylum in 1880 and again in 1881 (Arnold, 1992; letter 204; and letter 158 as amended by Hulsker, 1990). The hospitalization in The Hague took place when van Gogh was 29 years old. First indications of neuroses and psychoses occurred at age 27 (according to his fathers assessment). First expression of serious mental problems thus occurred late in the third decade of Vincents life. SIX MAJOR CRISES The last two years of van Goghs life included six well-documented medical crises with serious mental problems. The period under discussion, October 1888 to July 1890, is shown in Figure 1, which depicts calendar months (center line), sequential locations (bottom line), and the crises (stippled rectangles above the time line). Van Goghs suicide is marked with a Roman cross. The utility and power of the graphical presentation derive from the multiplicity of facts depicted and, in addition, from the visual summary (the Gesta¨lt). Thus we can see that the durations of the crises are variable (days, weeks, or months) and there is no discernible trend (the succeeding crises neither shorten nor lengthen in a regular manner). The five periods between major attacks show neither consistency nor trend. Their lengths were 38, 148, 116, 21, and 26 days. The range is large; the mean happens to be 70 days (standard deviation¼58 days). Vincent was a patient (voluntary inmate) at Saint Paul de Mausole Asylum at St. Re´my for just over a year (May 8, 1889 to May 16, 1890), although the initial plan had been for only three months. The attending physician, Dr. The´ophile Peyron (18271895), made occasional, spare notations in the register. Towards the end he wrote that the patient [van Gogh] . . . experienced during his stay in this institution several [medical] attacks with a duration of two weeks to a month. In reality, during the St. Re´my period with Dr. Peyron, the durations were 45, 7, 7, and 65 days in chronological order. The discrepancy suggests that Dr. Peyron was writing from memory, at some distance from the events. Van Gogh himself had not kept accurate records. In letter 631 Vincent wrote to brother Theo, I pointed out to [Dr. Peyron] that such attacks . . . have always been followed by three or four months [i.e. 90120 days] of complete quiet. I want to take advantage of this period to move [from St. Re´my to Auvers] The actual numbers were 70 58 days (see above). His last crisis at St. Re´my ended April 29, 1890. It is remarkable that a safe period of three months (Vincents intuitive but unsupported prediction) would literally terminate on July 29, 1890! The suicidal act (possibly inspired by an impending crisis) was committed on July 27. Each crisis had an abrupt onset and, at the end of days or weeks, a swift resolution. In some cases the artist even used words with the following implications one day fine the next day, down with sickness and yesterday I was too sick to write today I pick up the pen. It is worth Fig. 1. Time course of six major crises suffered by Vincent van Gogh. Details are given in the text. 26 WILFRED NIELS ARNOLD recalling how desperate the early prognosis about the December 1888 crisis had been. After Augustine Roulin (18521930) visited the hospital at Arles on the 27th, Vincent had increasing neurologic problems. The following day her husband Joseph Roulin (18411903) was unable to see him because van Gogh was suffering from aphasia. And then, on the last day of December, to the pleasant surprise of doctors and friends, the patient made a recovery so rapid and complete that Rev. Salles could report that he found him calm, in a state which revealed nothing abnormal (van Gogh-Bonger, 1978, xlvi). By the first week of January Vincent was moving around the hospital and conversing freely with Roulin and others, and even cautioning Theo not to alarm his mother and sister Wil. unduly (letter 569). On January 7, he returned to his home in Arles (made famous by his painting The Yellow House) and that day declared to his mother and sister that there is a chance that there will be nothing the matter with me for a long time to come (letter 569a). The periods between major attacks were remarkably normal. The lucidity with which the patient comprehended and wrote letters, discussed his condition with physicians, weighed the possibilities for the future, and maintained the quality of his art work, are all evident. From all indications (van Gogh, 1978; Tralbaut, 1981; Pickvance, 1984, 1986; Arnold, 1992), Vincent did not write letters and did not paint during crises. Unfortunately, this did not prevent future romantics (see for example Schnier, 1950; Navratil, 1959) from seeing disease in his art work! Potential precipitants of eight crises are summarized in Table 1; documentation will be provided later. The course of van Goghs illness is very instructive in approaching a retrospective diagnosis. The features are a guide to a working hypothesis that can then be either strengthened or challenged by further data. Hence any reasonable suggestion must first accommodate the kinetics and time course of van Goghs illness, and I would encourage organized skepticism in examining how poorly the observed data fit with ideas from the past. For example, we may ask whether a proposed medical entity usually presents with rapid (of the order of twenty-four hours) onsets and resolutions, or does the patient with the syndrome under discussion tend to drift through days or weeks into a debilitating episode and then later slowly emerge? Are the intervening periods marked by complete lucidity and impressive productivity or is there an indication of a cumulative neurological deficit and a mounting struggle to perform? Are the observed periods of Table 1. Precipitating Factors According to Arnold (1992). Date of crisis Location Precipitants 1880 The Borinage (Belgium) Fasting or general neglect of nutrition are possibilitiesa June 1882 The Hague (Holland) Gonorrheal infectionb December 1888 Arles (France) Alcohol (especially absinthe) February 1889 Arles (France) Camphor, fasting, alcohol (especially absinthe) JulyAugust 1889 St. Re´my (France) Alcohol (especially absinthe) consumed in Arles during a social visit December 1889 St. Re´my (France) Exposure to turpentinec January 1890 St. Re´my (France) Alcohol (especially absinthe) consumed in Arles during a social visit FebruaryApril 1890 St. Re´my (France) Alcohol (especially absinthe) consumed in Arles during a social visit. This crisis actually started in Arles Note. aPoorly documented, but related to the concerns of van Goghs father. bWe refer to the complication that followed the primary infection. cExpression of a pica (Arnold, 1988) for terpenes and terpenoid compounds: camphor, pinene (in turpentine), thujone etc. from absinthe. THE ILLNESS OF VINCENT VAN GOGH 27 pronounced illness for van Gogh compatible with a candidate disease, or would one expect minutes or hours months or years? With any of these other proposals, would attacks be precipitated by seemingly unrelated factors such as fasting, microbial infection or xenobiotics? All the while we must bear in mind that Vincents organized care during the medical crises of the last two years was practically limited to bed rest, one prescribed drug (potassium bromide), good nutrition, and restriction of alcoholic beverages. During van Goghs hospitalizations the attending doctors, nuns, and other attendants were essentially engaged in sympathetic nursing and patient-protection, in response to observation and concern. THE ROLE OF ABSINTHE Artists painted and poets personified; men and women embraced the ritual of presentation as well as the appearance, taste, and excitement of the liqueur called absinthe. Some of the most creative people of the nineteenth century were included. The aesthetics of absinthe drinking contributed to its popularity. Nevertheless, one looks beyond ethanol to the mood-altering chemicals that were unique to this alcoholic beverage in order to rationalize the volumes consumed in some quarters (Arnold, 1989). There was a fifteen- fold per capita increase in France from 1875 to 1913, when the national annual consumption attained a massive 9.7 million U.S. gallons. Whenever you have this many people imbibing a particular beverage, there must be more to it than poetry and attractive colors. In the department of Bouches-du-RhoË?ne, which includes van Goghs southern venues of Arles and St. Re´my, the annual consumption was an impressive 2.45 liters per head, which was more than four times the national average (Schmidt, 1915). VINCENT VAN GOGH AND THE INDIVIDUAL RESPONSE Some years ago, while perusing the letters of Vincent van Gogh, I was intrigued by the chemical connection between absinthe constituents (such as the toxic compound called thujone) and some other terpenoid compounds in his life. These exposures involved Vincents use of massive amounts of camphor to combat insomnia, an attempt to drink essence of turpentine (pinene), and references to his nibbling at oil colors (mixed with turpentine). The possibility of an interaction became more compelling when I read Sollmann (1948) on thujone and camphor, wherein he remarked that the convulsions induced in experimental animals are antagonized by bromide, while the threshold is lowered by nicotine. While institutionalized in Arles, van Goghs crises were ameliorated by taking bromides and decreasing smoking. Accordingly I suggested that van Gogh had developed an affinity or a pica for terpenes, the documented examples being thujone, camphor, and pinene (Arnold, 1988).8 This would help to explain some of the strangest of van Goghs acts during his last two years his attempts to eat his paints and to drink turpentine and kerosene which were previously regarded as absurdities and unrelated. The response to any drug or xenobiotic depends upon a variety of factors not least of which the nutritional status of the subject. For example, an increased toxicity of camphor and related compounds is noted during fasting and is attributed to a compromise in glucuronic acid formation (Sollmann, 1948).9 Infections and unerlying illness also play critical roles in determining the individuals response to drugs. There are several indications in his letters and in painted objects that Vincent developed an affinity for absinthe. He painted The Night Cafe on the spot, staying up three nights in a row and sleeping during the day (letter 533). It is tempting to speculate that he had a glass or two during the execution of this painting; he certainly had access, and the landlord was apparently pleased with the whole event. Apart from the 8Pica comes from the Latin for magpie, a bird who carries away odd objects. In medical terminology it refers to compulsive eating of non-nutritive substances and has been ascribed to various disorders including malnutrition. 9Camphor is secreted in the urine as hydroxycamphor glucuronide. 28 WILFRED NIELS ARNOLD possibility of this special case, we do not imply that van Gogh painted while intoxicated. There has been much discussion on the amount of absinthe (and other alcoholic beverages) consumed by Vincent in Paris, Arles, St. Re´my, and Auvers. At one extreme we have Jan Hulsker who steadfastly maintained that Vincent was not a drinker (Hulsker, 1990). In an earlier publication (Arnold, 1988) I described a pastel by Toulouse- Lautrec and mentioned that it depicts Vincent partaking of a glass of absinthe. Hulsker (1990, pp. 401404) objected to partaking and insisted on the static message that Vincent only sits before the glass. That Toulouse-Lautrec chose to depict Vincent with a glass of absinthe suggests to me that it was a common enough circumstance, and that Vincent drank absinthe. We feel that van Gogh was not in the habit of simply decorating his table with a glass of absinthe in front of him as Hulsker would have it (Hulsker, 1990, p. 322). That commentator maintains the isolated position that there is no evidence that van Gogh was fond of absinthe, and he also denies all the statements and anecdotes about his drinking problem. Alas, Hulsker defeats his own hypothesis in several places, not least of which when he suggests that Vincents lack of recall of the ear-cutting episode was because drinking had caused him to black out (Hulsker, 1990, p. 322). At the other extreme we have those reporters with a list who would include absinthe abuse as a free-standing explanation for all of Vincents problems. Other commentators, who had been told that their initial hypotheses didnt accommodate all of van Goghs signs and symptoms, subsequently invoked absinthe as a rider. I provided a concordance on Vincents references to alcohol, including letters in which he expressed fear of becoming an alcoholic (Arnold, 1992, p. 79). Paul Gauguin (18481903) lived with van Gogh during the two months running up to Vincents first crisis in Arles. Anecdotes suggest that Gauguin consumed at least as much absinthe as van Gogh, but he did not exhibit the same medical problems. If so many were drinking absinthe, why did his neighbors (letter 579) regard Vincents behavior as so bizarre? The explanation that has escaped most reviewers is that Vincent was abnormally sensitive to absinthe, even in the amounts associated with social drinking, because of his congenital illness. Absinthe is but one factor in the environmental impact on Vincents underlying illness; it also comes under the category of lifestyle. Hemphill (1961) deserves much credit for being the first to consider absinthe as an external chemical influence on van Gogh. Vincent himself seemed to be approaching this idea when he wrote, it seemed to be caused more by some outside influence than by something within myself (letter 605). Loftus and Arnold are convinced that it was the underlying illness of acute intermittent porphyria that made Vincent so sensitive to absinthe and malnutrition. ACUTE INTERMITTENT PORPHYRIA (AIP)10 AIP is one member of a class of metabolic abnormalities, the porphyrias, which are characterized by the excessive production of porphyrins, or related compounds (Waldenstro¨m, 1957; Kappas et al., 1989). Individuals who suffer from these diseases are prone to excrete elevated concentrations of these same compounds in their urine and feces. The abnormal excretion per se is of no intrinsic medical import but it is a reflection of elevated concentrations circulating within the body, and therein lies the potential for cutaneous photosensitivity (due to porphyrins), neurological abnormalities (due to porphyrin precursors), or both. In the case of AIP, all of the symptoms are neurological and the specific, overly-produced compounds are d-aminolevulinic acid and porphobilinogen. These are intermediates in the metabolic pathway to porphyrins, which in turn are used in the biosynthesis of the heme of hemoglobin, and other heme-containing proteins. Acute refers to the rapid onset, and abrupt cessation, of expressed symptoms. (The underlying cause of AIP is present from birth, so in that sense it is chronic.) 10Please consult my book (Arnold, 1992) for a much fuller discussion of acute intermittent porphyria. Only the most salient primary references will be given here. THE ILLNESS OF VINCENT VAN GOGH 29 Intermittent refers to the periodicity, which is typical, and emphasizes the distinct periods of normalcy which intercede between the episodes of illness. Symptoms rarely occur before puberty; the peak decade for onset of symptoms is from age 20 to 29 (somewhat later for males than females) but the disease sometimes remains latent throughout a lifetime (Waldenstro¨m, 1957). Tabulations of the most common hallmarks emphasize abdominal pain and other gastrointestinal complaints, symptoms referable to the peripheral and central nervous systems, and signs of autonomic neuropathy including tachycardia and hypertension. Porphyria-induced hypertension can cause early-onset renal failure (Laiwah et al., 1983). Bladder dysfunction may result in urinary retention (Laiwah et al., 1983; Kappas et al., 1989). Effects on optic nerves or the occipital lobes have been documented for AIP cases (Ridley, 1969). Sexual impotence (Kappas et al., 1989) has occasionally been reported. Premonitory symptoms include restlessness and irritability; attacks develop rapidly; resolution may occur in days or sometimes weeks, in an unpredictable fashion. Seizures do not always attend severe crises, but when they domany antiseizure drugs, with the notable exception of bromides, may adversely affect the outcome (Bonkovsky et al., 1980; Moore, 1980). The unpredictable nature of the disease with respect to both onset of crises and outcome makes an acute attack of AIP particularly treacherous. It can be one of the most terrifying experiences imaginable. Patients can become almost completely paralyzed in severe cases. They are unable to breathe, swallow or communicate properly, yet remain conscious for some time, all the while suffering pain, being aware of their plight, and wondering if it will ever end. The most common cause of death from AIP is respiratory paralysis. Most importantly, the expression of neurological and other symptoms depends upon lifestyle and exposure to precipitating factors. Early examples of AIP were revealed as a response to new drugs; initially the hypnotic Sulfonal (2,2-bis (ethyl sulfonyl) propane), later barbiturates; and subsequently many other drugs, alcohol, and sundry organic compounds (Moore, 1980). Some steroid metabolites precipitate attacks, and endogenous changes may account for some crises at puberty and the earlier onset with females. Other exacerbating factors include infections and malnutrition (Kappas et al., 1989). Low-carbohydrate and low-protein diets are especially detrimental (Welland et al., 1964) and fasting can precipitate an attack of porphyria (Knudsen et al., 1967). A study in Scotland indicated an association between smoking (nicotine is metabolized via cytochrome P450) and the induction of repeated attacks in patients already diagnosed with AIP (Lip et al., 1991). Even an excess of coffee may be a problem because caffeine is also porphyrogenic (Moore, 1980). VINCENT VAN GOGH AND AIP All of the hallmarks of Vincents illness can be accommodated within this overview of AIP. The most important and well documented are the gastrointestinal complaints, neurological disturbances, age of onset, jagged time course, and the exacerbations caused by inadequate nutrition and absinthe abuse. Other aspects such as sore throats, eye problems, fevers, a bout of aphasia in the Arles hospital, and impotence, have other possible causes but are all compatible with underlying AIP. Van Goghs smoking habit may have contributed to recurrent attacks. Vincents urinary tract infection in The Hague may have precipitated an AIP crisis leading to the complication and extended hospitalization at that time. It is also possible that his urinary retention recorded at that time was exacerbated by an AIP attack. Arnold (1988) suggested that van Goghs fondness for absinthe developed into a pica for terpenes, the documented examples being thujone, camphor, and pinene. It is worth noting that 1,8 cineole, a constituent of crude camphor and wormwood oils, is a proven precipitating agent for AIP (Bickers et al., 1975). Van Gogh used reckless doses of camphor oil against insomnia (letter 570) and absinthe contained a variety of essential oils including wormwood. Bonkovsky and Arnold have shown that camphor, thujone, and pinene are porphyrogenic (Bonkovsky et al., 1992). The combination of overexposure to camphor, absinthe abuse, and fasting or 30 WILFRED NIELS ARNOLD malnutrition would be injurious for anyone, but devastating for someone with AIP. Loftus and Arnold (1991) believe that all recorded signs and symptoms of Vincents illness can be accommodated by acute intermittent porphyria. Arnold (1992) presented cases of AIP from the 20th century that had analogies to the illnesses of Vincent, Theo, and their sister Wil. (1862 1941). It behooves proponents of other hypotheses to provide similar case histories, complemented with the diagnostic insights ofmodernmedicine, to either support or damage their alternatives. THE BIOCHEMICAL LESION IN AIP Almost any cell in the human body can engage in synthesis of heme because it is not only vital to hemoglobin but also for the cytochromes involved in so many aspects of metabolism. The biochemical pathway to heme consists of eight enzymes and an exquisite control mechanism. A partial deficiency (about half of normal) of enzyme (catalyst) number three (porphobilinogen deaminase) in this sequence is the underlying cause for the manifold derangements of the AIP patient under crisis. The organ of primary concern for this inherited disease is the liver, where two thirds of the heme that is produced is incorporated into the various types of cytochrome P450. An even larger proportion attains during the induction of P450s, which attends the livers encounter with xenobiotics. The AIP patient has a vulnerable heme pathway. The neurological problems associated with medical attacks are a consequence of upsetment of the heme pathway and the toxic accumulation of two intermediate compounds, daminolevulinc acid (ALA) and porphobilinogen. Because porphobilinogen deaminase is not ratelimiting to the overall pathway, 50% of normal is sufficient for unstressed AIP patients. This explains the lack of symptoms for latent AIP patients and the intervening periods of normalcy for patients who have experienced periods of sickness. It is the first enzyme in the pathway, ALA synthetase, that is normally rate-limiting. Therein lies the major control feature because heme (the end product of the pathway) causes both a repression and an inhibition of ALA synthetase. When the heme concentration of liver cells is depleted, the effective amount of ALA synthetase may be increased over ten-fold. Under those circumstances the partial road block at enzyme number three for AIP patients is felt, and toxic levels of the preceding compounds are produced. Ingested compounds that are metabolized via cytochrome P450s in the liver deplete the heme pool and induce the synthesis of ALA synthetase. These include alcohol, many drugs, and many xenobiotics (Moore, 1980). The van Gogh terpenes (camphor, thujone and pinene) can be added to that growing list (Bonkovsky et al., 1992). On the other hand, synthesis of ALA synthetase can be decreased by high glucose intake, thus helping to explain the ameliorating effect of a high carbohydrate diet on AIP attacks and the adverse effect of malnutrition or fasting (Kappas et al., 1989). More extensive discussions of the heme pathway are given elsewhere (Kappas et al., 1989; Arnold, 1992) and further pursuit of the biochemistry is not appropriate to this review. However, I would like to offer an hydraulic model of the control mechanism to assist the non-chemical reader. The diagram on the left of Figure 2 represents each intermediate compound (a,b,c . . . heme) as a solution in a cylinder being acted upon by an enzyme (exit tube) as it passes on to the next vessel. The AIP patient has about half the normal amount of the third enzyme (exit partly closed by the bold arrow). But the overall flow is steady thanks to regulation of the first enzyme (the float mechanism senses the level of the heme pool). The diagram on the right depicts the consequence of depleting the heme pool (pulling the plug): the activity of the first enzyme increases greatly (increased drop-size in the model) and now the partial block at the third enzyme (in the AIP patient) comes into play. Compounds c and d accumulate and will spill-out (X). Only under a crisis does the AIP patient excrete large amounts of d-aminolevulinic acid (compound c) and porphobilinogen (compound d) in the urine. Even then the freshly voided urine is of normal color, but with time these compounds polymerize to form porphobilin which imparts a brown or red (the color of porphyry) pigmentation to aged specimens. The final color is influenced by concentration, pH, light, oxygen and temperature. THE ILLNESS OF VINCENT VAN GOGH 31 The propitious availability of a porphyric urine sample together with the low-tech windowsill test can be very instructive in the diagnosis of AIP. Urine which has aged internally due to bladder dysfunction may already be discolored when released with a catheter, although the color is sometimes mistaken for urinary tract bleeding. In contradistinction to the claim that port wine urine is the faithful telltale sign of AIP, it is worth emphasizing that many 20th century carriers with documented medical attacks have never remarked upon abnormally colored urine because it was either not saved or not aged. Dark or red urine is not mentioned in the published van Gogh letters but this really does no damage to the AIP hypothesis.11 Barker and Estes (1912) were the first to note that AIP runs in families. The extensive studies of Waldenstro¨m (1937) in Sweden firmly established the inherited nature of the disease. The disease follows an autosomal dominant pattern of inheritance; if one parent is a carrier then on the average 50% of the children will bear the defective gene (Kappas et al., 1989). However, the penetrance is variable, so that in some families only a fraction of the carriers actually express signs and symptoms of the disease (Gates, 1946). Vincents mother died at 88, having led a seemingly healthy life. His father, the Reverend Theodorus van Gogh, died at 63; his studies for the church had been interrupted by serious illness; he was judged not to have been in very good health most of his life (Tralbaut, 1981). It is believed that he died from a stroke and, because hypertension is present in over half of AIP patients (Goldberg, 1985), this underlying disease would be one of many possibilities compatible with that cause of death. Of Vincents parents the father may be the more likely (obligate) carrier of AIP, but this is little more than an educated guess. He led a careful and balanced life in his post in the wilderness (Tralbaut, 1981) and may have avoided the Fig. 2. An hydraulic model for the control mechanism in the heme pathway. Details are given in the text. 11Critics of the AIP hypothesis for Vincent have occasionally pretended that this was a serious deficiency. It is negative evidence at best but can be rationalized. Vincents accommodations were often primitive by todays standards; for example, the Yellow House in Arles had no toilet and he used the facilities at the hotel next door (letter 480). He relieved himself in the field while painting. Moreover, even if he encountered reddish urine he may well have attributed it to blood, given his experiences with catheters and bougies at The Hague (letter 209). 32 WILFRED NIELS ARNOLD precipitating factors that affected three of his six children. There were numerous exchanges between the brothers concerning their nervous problems. It is not clear whether Theos serious illness at age 19 was related to the expression of AIP-like symptoms, but certainly by December 1886 (age 29) according to his future brother-in-law, Andries Bonger, he had serious nervous complaints, so bad that he could not move (Hulsker, 1990, p. 455). Theo seems to have been in reasonable health at the time of Vincents funeral. But two months thereafter Theo suffered further leg pains and also hallucinations (partly in response to an unspecified medicament for his cough), became very irritable and occasionally violent, muttered with difficulty in mixed languages, experienced urine retention, and was totally unconscious with a barely detected pulse before he died (aged 34) (Rewald, 1986, p. 69; Hulsker, 1990, p. 455). Leg pains, mental illness, and paralysis would all support a diagnosis of AIP, and the violent reaction to a new drug and renal failure would be in accord with AIP (Arnold, 1992). On the other hand the reversibility of the leg pains does not support the diagnosis of neurosyphilis offered by Dr. Frederik van Eeden.12 Vincents youngest sister, Wil., spent the latter half of her 79 years in an asylum for psychiatric cases. She may also have suffered from AIP, although the lack of further documentation makes her case much more speculative. The youngest brother, Cor, died at 33 in South Africa from an accident while feverish; it may have been a suicide. Again, the medical history is scant. His other sisters, Elizabeth and Anna, lived 77 and 75 years respectively, without any indication of medical crises (Arnold, 1992). Loftus and Arnold (1991) and Arnold (1992) discussed the differential diagnosis of Vincent van Gogh in favor of acute intermittent porphyria. We hoped that the facts would speak for themselves and that informed readers would have no difficulty in rejecting other hypotheses.13 In the decade that followed there was no new hypothesis, but we encountered ongoing competition from several old ones, whose authors were occasionally quite vocal via the popular media. It is beyond the scope of this review to look back on more than a selection of these. VINCENT AND EPILEPSY? Epilepsy is defined as a paroxysmal (sudden and recurring) transient disturbance in brain function that is manifested by episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. The derivation of the word is Greek; it means seizure. Accordingly, the term epileptic seizures is redundant, but common parlance. Another basic term is convulsion, which means a violent involuntary contraction, or series of contractions, of the normally voluntary muscles. Niedermeyer (1983) emphasized that epilepsy is not a disease but rather an abnormal reaction of the brain due to numerous causes. Several diseases and conditions are complicated by seizures and convulsions. They may accompany withdrawal from alcohol or barbiturates and attend uremia. Other acute illnesses which present with seizures include hyponatremia, thyrotoxicosis, the acute porphyrias, and hypoglycemia. Lead and arsenic are the most frequently encountered metallic intoxications which cause convulsions. Tonic-clonic convulsions were not described by Vincent or his doctors, so grand mal seizures have never received much diagnostic support. Petit mal or absence seizures (a brief lapse in 12Theo died at Willem Arntsz Stichting, near Utrecht, on January 25, 1891. The local diagnosis was neurosyphilis. This item was discovered 100 years later by Dr. A. Pietersma, Archief Dienst Gemeente, Utrecht. 13Informed readers turned out to be a bigger assumption than anticipated. A fatuous example came from an East-Coast psychiatrist who wondered if the subsequent lack of reference to our work is related to it being published in The British Medical Journal, a journal that is not widely read in the U.S. and your main thesis being published in a monograph (private correspondence). THE ILLNESS OF VINCENT VAN GOGH 33 consciousness usually no longer than twenty seconds) are certainly not indicated. Thus the classical sorts of epilepsy, which were well understood in Vincents time, were hardly indicated. For this reason I agree with Tralbaut (1981) that Dr. Peyrons unqualified diagnosis of epilepsy in the St. Re´my register was based upon the patients preconceived, ill-informed view.14 If indeed Drs. Rey and Urpar (Arles), and Peyron (St. Re´my) were convinced that Vincent van Gogh had some sort of epilepsy, then why wasnt he treated for it?15 Admittedly the available therapy was meager, but Vincent was not even treated symptomatically at St. Re´my, and no advice along those lines was passed on to Paris when Vincent departed. Contrast Vincents casewith that of Fyodor Dostoevsky (18211881) who wrote, on June 17, 1863, I go to Paris and Berlin . . . only for consultation of specialists (Trousseau in Paris, Romberg in Berlin) for my epilepsy (Voskuil, 1983, p. 665). If they really thought he had epilepsy, it is curious indeed that Vincent, a quarter of a century later, was not referred to an epilepsy specialist at Montpellier or Paris! As early as the 1870s, Hughlings Jackson had described certain hallucinations with seizures that he related to a pathologic condition of the temporal lobe (Jackson, 1931). Later, so-called psychomotor seizures were well described (Gibbs et al., 1937). In the 1950s the anatomical adjective temporal lobe was again preferred, even though some other parts of the brain were sometimes involved (Penfield & Jasper, 1954). Today, these are all lumped under complex partial seizures (Gastaut, 1970). Dr. Edgar Leroy, who worked at St. Re´my Asylum, albeit many years after van Goghs sojourn, and Dr. Victor Doiteau considered that Vincent was epileptic but found no evidence of aura or frank convulsions and suggested temporal lobe epilepsy (Doiteau & Leroy, 1928). See also Vinchon (1960). A diagnosis of temporal lobe epilepsy might explain Vincents hallucinations, the episodic nature of his illness, and the interictal periods of normalcy. However, the usual duration of minutes or hours that attends the various forms of complex partial seizures does not fit the days and weeks of Vincents crises. More importantly, epilepsy does not accommodate the numerous gastrointestinal complaints. Likewise, some of the factors which exacerbated his illness such as malnutrition and fasting are not noted for inducing temporal lobe epilepsy. Drug therapy in the 1880s was limited, but Vincents fits and confusion (letter W11) seem to have been controlled in Arles by bromide (letter 574), which would be indicated for absinthe intoxication or acute intermittent porphyria, but not for temporal lobe epilepsy. Bromides are effective against grand mal and simple partial seizures but not for complex partial seizures (Hemphill, 1961; Niedermeyer, 1983). Monroe (1978, 1992) noted that the limbic system is exquisitely sensitive to stress and external toxins including alcohol, and he remarked on Vincents affinity for absinthe. This was rediscovered by Blumer (2002), who was adroit in avoiding all the data on van Gogh that did not fit temporal lobe epilepsy. MANIC-DEPRESSIVE ILLNESS (BIPOLAR AFFECTIVE DISORDER)? The assumption made by some commentators that manic-depressive psychosis was unknown in Vincents day is incorrect. Falret (1854) had described so-called circular insanity in which mania and melancholia alternated at regular intervals. Note that the term melancholia was still used, but the meaning was by then approaching a modern definition of depression.16 The same 14Tralbaut felt that the doctors at Arles and St. Re´my were sympathetic to van Goghs suffering but not particularly interested in taking a complete medical history. My impression is that they were completely baffled by Vincents illness. 15Claims (Gastaut, 1956) that Felix Rey (a young intern still in training) was ahead of his time, and that his friend Aussoliel was a local expert on masked epilepsy, are not convincing. 16The first good description of a relationship between mania and melancholia came from the Englishman ThomasWillis (16211675), who mentioned that one can change into the other . . . this cyclic disorder is like a burning object, one that can produce smoke or flame (Willis, 1672; Finger, 2000). 34 WILFRED NIELS ARNOLD year, Baillarger (1854) also wrote about these two states, and also included an intercalated period of normalcy as an integral part of the syndrome. It should be mentioned in passing that Dr. Paul Gachet attended lectures by both Falret and Baillarger.17 A protracted dispute over priority ensued, although it would seem that Baillargers double-form disease was closer to our present concept (Kra¨pelin, 1921) of manic-depressive psychosis or bipolar disorder. The French Academy of Medicine had major meetings on the subject starting in 1880. How well it was recognized, received, or dealt with in Arles and St. Re´my in 1889 and 1890 is an open question, especially as to the intent of Drs. Urpar and Peyron when they used the term acute mania. I am inclined to think that they were referring to the December 1888 events in and around the earcutting incident and Vincents first hospitalization, and then the complaints of neighbors about Vincents drinking sprees which led to his readmission to the Arles hospital in 1889. If that is true then it was old fashioned mania a la Pinel.18 By 1900 mania had assumed its present psychiatric meaning of a mood disorder characterized by expansiveness, elation, agitation, hyperexcitability, hyperactivity, and increased speed of thought and speech (flight of ideas). Up until the beginning of the 19th century, the prime meaning of melancholia was intensity of idea, the image of the mind being strongly fixed on, and frequently returning to, a single set of ideas, to an extent that was deemed unhealthy. The connotation of sadness was not always present, and many forms of behavior that have little relationship (from our perspective) were included in the general class of melancholia. Not surprisingly there was even a productive melancholia that today might be more akin to intense, creative, concentrated thinking directed at a particular problem, while excluding all day-to-day distractions (monomania). Thus melancholia moved through monomania to depression and it is difficult to gauge how far Dr. Peyron had progressed.19 Perry was probably the first to discuss manicdepressive psychosis as a diagnosis for Vincent van Gogh; her expression was cyclothymic personality with episodes of depression and mania (Perry, 1947, p. 171). In the opinion of Hemphill, van Gogh was a manic-depressive who developed confusional episodes and fits in the last two years of his life due to the toxic action of thujone, the active agent of absinthe (Hemphill, 1961, p. 1084). Hemphills contribution was twofold; he was the first to correctly refer to Vincents epilepsy as a disorder rather than a disease, and he stressed the evidence for a toxic psychosis. He supposed that the gastrointestinal complaints came from the absinthe abuse alone, whereas Arnold and Loftus stress van Goghs sensitivity to absinthe (and other xenobiotics) due to the underlying disease of acute intermittent porphyria. Other writers have marched Vincent down the bipolar trail but have discovered nothing new since Hemphill (1961). Manic depressive illness is widely diagnosed today and a significant part of the pharmaceutical industry is devoted to discovering further chemical assists for the sufferers. These patients are rarely aware of their states and ordinarily do not check themselves into hospitals. Their disorders do not have acute onsets and offsets and the time course of van Goghs illness certainly does not fit that syndrome. However, it is common enough for artists and museum patrons to know, or think they know, something about the syndrome and someone in their immediate circle who has it. Proponents of this working hypothesis exploit this statistical swell even though they should be arguing about the illness of just a single individual, Vincent van Gogh. 17The title of Dr. Gachets thesis was E ´ tude sur la Me´lancolie (Gachet, 1858). The work was written in 1858, in the middle of this transition period in terminology. His thesis was really a compendium of principles for moral treatment of the insane, spiced with a philosophical vitalism that he encountered at the Montpellier Medical School (Fabbri, 1966). 18In Pinels book (1818), mania was a disorder of one or more faculties with sad, gay, extravagant or raging affect, but always included blind aggression. 19The´ophile Peyron (18271895) made his first medical career in the navy and then settled in Marseille as an oculist. His appointment as director at the asylum of St. Re´my may have been a semi-retirement position, as Vincent hinted (letter 593). THE ILLNESS OF VINCENT VAN GOGH 35 A course of regular cycling between mania and depression, which is popularly held, is rarely observed (Sarwer-Foner, 1966). On the average there are nine to ten depressive episodes for every manic event. A histogram of overall frequency versus age-of-onset for manic-depressive patients [n¼898] peaked with the 1519 year group, and was closely followed by the 2024 year group (Goodwin & Jamison, 1990). Notwithstanding considerable searching, biochemical and genetic markers for bipolar affective disorder have yet to be found. It has been widely observed that many creative people had illnesses that were serious, debilitating, and sometimes limiting to their productivity. The majority opinion is that these men and women were successful in spite of illness, and not because of it. It is also true that many creative people enjoyed robust and healthy lives.20 During the 18th and 19th centuries there lived an unfortunate philosophy relating the fevers of tuberculosis to activities on a higher plane. This romantic notion has now fallen by the wayside, but during the last twenty-five years manic depressive psychosis has popped up and down as a fashionable disease of association with creativity. Andreasen (1987) evaluated 30 faculty members, over a 15-year period, at an American university workshop for creative writing. She claimed that the writers had a substantially higher rate of mental illness compared with 30 control subjects matched on sociodemographic grounds. A higher rate of affective disorders, especially manic depressive psychosis, was reported for the so-called creative group as well as their firstdegree relatives. Jamison (1989) reported that 38% of a British group consisting of 39 writers and 8 artists, which she deemed outstanding, had sought treatment for some form of affective disorder, especially manic depressive psychosis, compared with lifetime prevalence rates in that nation of about 6%. Her attempts to link hypomanic episodes and seasonal mood swings with productivity were unconvincing. Rothenberg (1990) criticized both the Adreasen study and the Jamison follow-up on the grounds that little consideration was given to the subjects reasons for participating in the studies, and the criteria for judging them creative were left unexplained. Furthermore, Andreasons self-reliance on evaluation of relative mental health was potentially biased because the subjects and controls were already known to her. And Jamison built her case on the subjects own reports of seeking medical treatment. Goodwin and Jamison (1990) came up with a list of people they judged to have been creative together with an indication (opinion) that they suffered from manic depressive illness. The cautious message from all of this should be that such a debilitating condition is still compatible with creativity, but in some circles there has been an inference of causality.21 For example, Jamisons book on manic depressive illness and the artistic temperament (Jamison, 1993) certainly leaves the reader with the indication that the creative are more susceptible to manic depressive illness than the normal run of people, and the impression that a sort of Faustian bargain is at play. SCHIZOPHRENIA? Progressive changes in content and style have been observed in the work of artists who are deemed to have schizophrenia (Prinzhorn, 1972). The reverse namely to see the psychosis in unknown artists by looking at their work is obviously more difficult, but not sufficiently daunting to inhibit the proponents of schizophrenia for Vincent van Gogh. Such was the approach of Jaspers (1922), who is still quoted under this heading. Vincent had hallucinations, and he also had at least one episode of paranoia when he thought that neighbors were trying to poison him in Arles, but these are not specific for schizophrenia. The progressive deterioration of the untreated 20There have been some futile attempts at constructing ratios. My friend Don Goodwin accused them of playing a floating game as they found more candidates to be healthy they would add others to the numerator by sticking them with illness labels. 21There is also some overlap here with Dr. Gachets thesis list of outstanding individuals who suffered from melancholia (Gachet, 1858, pp. 922). 36 WILFRED NIELS ARNOLD schizophrenic is lacking in van Gogh. Perry remarked that [Vincent] did notwithdraw from the world; he was cast out because of his behavior (Perry, 1947, p. 162). The schizophrenic has a decrease in affect whereas Vincents letters and pictures were surcharged with emotion. Hemphill (1961) saw no sign of schizophrenia in the artist and emphasized that there was never any fantasy formation, and that his letters were lucid and logical. There is no case for schizophrenia (Arnold, 1992). NEUROSYPHILIS? Syphilis can be acquired either congenitally or, most often, by sexual contact with an infected individual. The primary stage is remarkably free of systemic signs, the patient is entirely well and usually free of fever but, at about 112 weeks after contact, 50% of females and 70% of males develop a primary lesion (chancre) at the site of infection by the spirochete Treponema pallidum. In the secondary stage, at 212 weeks after the primary stage, a skin rash appears. Constitutional symptoms that may accompany secondary syphilis include fever, weight loss, malaise, and anorexia. There follows an asymptomatic latent stage that may last decades. About 30% of untreated patients go on to develop tertiary lesions, but clinical disease occurs in only half of these cases; this fraction is 15% overall. About 80% of the tertiary lesions affect the cardiovascular system, 10% are chronic focal inflammations (gummas) in the liver and other sites, and up to 10% involve the central nervous system (neurosyphilis), i.e. 1.5% overall (Robbins, 1957). The major clinical categories of symptomatic neurosyphilis are meningovascular and parenchymatous syphilis. The latter includes tabes dorsalis, characterized by degeneration of the posterior columns of the spinal cord and posterior spinal roots. The interval from infection to expression of symptoms is about 27 years. Another form of parenchymatous syphilis, general paresis of the insane, is associated with direct invasion of T. pallidum into the brain. For unknown reasons the syndrome is more common in males. The average interval from infection to onset of general paresis is 20 years. The course of the untreated disease is inexorably progressive (Goodman & Karakuis, 1988). Neither the gamut of his symptoms nor the time course of his crises fits neurosyphilis. Vincent was treated for gonorrhea in The Hague in mid-1882 at age 29. He may have had a recurrence in Antwerp in 1885-86, at age 32. Even if he had contracted syphilis in The Hague, the major crises in Arles (age 35) would have been extraordinarily early for the onset of neurosyphilis, and his lengthy remissions from illness also negate the possibility. Mercury treatments were used at Arles and St. Re´my for syphilis, but Doiteau and Leroy (1928) found no indication that Vincent received mercury. LEAD POISONING About one-third of patients with excessive exposure to lead suffer colicky, abdominal pain. Fatigue, joint pains, headache, and irritability are also quite common. Impotence, constipation, vomiting, diarrhea have all been observed to some extent. Subtle effects on personality, memory, and learning ability are frequently associated with chronic lead poisoning. However, seizures and confusional states are less common, especially in adults (Dagg et al., 1965; Ellenhorn & Barceloux, 1988). Lead may be the oldest recognized chemical toxin; reports of occupational lead poisoning date to ancient Greece, and toxic levels have been found in Egyptian mummies. Artisans of leadglazed pottery and stained glass were particularly susceptible to intoxication until better conditions were adopted in the workplace. The ingestion of paints containing lead pigments has, even in recent times, presented a serious health hazard for children. Artists and craftsmen were exposed in the past because of their habit of wetting brushes orally and their accidental ingestion of lead-containing pigments from their tools and hands. Lead has an affinity for functional sulfhydryl groups in enzymes generally and a particularly sensitive example is d-aminolevulinic acid dehydratase. This is enzyme number two in the heme THE ILLNESS OF VINCENT VAN GOGH 37 biosynthetic pathway and its inhibition accounts for excessive excretion of d-aminolevulinic acid in the urine of lead-intoxicated patients. The last enzyme in the pathway, ferrochelatase, which catalyzes the incorporation of iron into protoporphyrin to form heme, is also inhibited by lead and this also contributes to the observed anemia (Ettenhorn & Barceloux, 1988). The excessive production of d-aminolevulinic acid in lead poisoning is similar to that found in acute intermittent porphyria, but note that porphobilinogen does not accumulate in lead poisoning. The similarity in neurological symptoms between AIP and lead poisoning may be referable to d-aminolevulinic acid. Abdominal pain, constipation, vomiting, paralysis, or paresis are very common in both AIP and lead poisoning. Neuropsychiatric symptoms are sometimes observed with lead intoxication, but much less frequently than in acute intermittent porphyria (Sassa, 1978). There was no chelation therapy for lead poisoning in Vincents time, and if his ingestion of lead salts (from his pigments) had been chronic, then the time course of such an illness would have been relentless and not episodic, as is well documented for van Gogh. ALCOHOLISM The extent of Vincents drinking is difficult to define, but we do know that he admitted to excesses. It is assumed that the hospital in Arles and the asylum at St. Re´my endeavored to restrict alcohol consumption; how successful they were is open to question; we do know that Theo paid a little extra at St. Re´my so that his brother could have wine with meals. I am convinced that Vincent engaged in social drinking when he visited friends in Arles, but this was for a relatively short time of a day or so. The time course of his illness, and the duration of some of the crises in the asylum, do not fit alcohol withdrawal syndrome per se.22 I believe it was more of a sensitivity to alcoholic beverages than an extraordinary dose. Alcohol is a an exacerbating factor for acute intermittent porphyria. Alcoholism and lead poisoning are reasonable suggestions but not standalone syndromes for van Gogh it is even less likely that the medical problems of Theo and sister Wil. would find much accommodation here. ME´NIE`RES DISEASE In 1861, Prosper Me´nie`re published several papers relating his observations on afflictions of the inner ear which caused nausea, vomiting, and vertigo. The disease was subsequently named after him and is characterized by hearing loss, vertigo, and tinnitus (ringing in the ears), and is usually unilateral (Harker & McCabe, 1980). During an attack of vertigo the patient is completely oriented to his surroundings and has no neurologic deficit such as paresthesia, diplopia, loss of consciousness, weakness, or paralysis. Sounds are distorted in the affected ear and are perceived as tinny. Loud sounds are intolerable or even painful, and hearing acuity gradually declines. Yasuda (1979) wondered in print, Was van Gogh suffering from Me´nie`res disease? The twelve page article was published in Japanese, but contains a full two pages of introduction and summary in English, more than enough to grasp the authors thrust. Those speculations received little support twenty years ago, because the diagnosis of Me´nie`res disease was based on a limited selection of symptoms. This dubious diagnosis was a sincere attempt, but it received little attention subsequently, except to be recorded in the most comprehensive bibliographies. The Journal of the American Medical Association, during the week of the centenary of Vincent van Goghs death, declared that, Van Gogh had Me´nie`res disease and not epilepsy (Arenberg et al., 1990). It was wrong on both counts; there is no case for Me´nie`res disease and epilepsy was no longer even the diagnosis of merit. A Colorado ear specialist and his colleagues had rediscovered Yasudas hypothesis and rewrote it as a definitive diagnosis. Their conclusion was based on a limited selection of symptoms, the pretense that 22Alcoholic seizures (rum fits) and delirium tremens occur after a heavy drinking bout. It is the signs that attend withdrawal that have some overlap with Vincents illness. 38 WILFRED NIELS ARNOLD epilepsy was the only viable alternative, and their propensity for construing certain complaints as hallmarks of the ear disease. Thus van Goghs gastrointestinal problems were taken to be strictly nausea and vomiting, several references to hearing voices were relegated to tinnitus, and the psychosis that was grave enough to cause selfmutilation and eventual suicide was underplayed. Their claim that van Gogh severed the lower half of his left ear to relieve tinnitus must surely strike readers, if not the editors of JAMA, as misplaced surgery.23 TOKENS There are many other working hypotheses by authors who are distinguished more by their conviction than common sense. Call-in talk shows on the radio are frequently their birthplace. Shortly after the publication of my book I encountered borderline personality disorder for van Gogh, which may be the exemplar for this type of offering. I thought that the title was enough to give the concept away but, to my astonishment, literature searches now turn it up in the form of published papers. The replacement child sentiment is another one in the same vein.24 I would continue to encourage organized skepticism as the first test. THE CHARM OF THE PAST There is an informal group that is keen to applaud the diagnostic skills of Vincents attending physicians. The old guys had it right after all is their banner. In their sea of indecision (sincere or deliberately compounded) this affords an island of safe haven blessed with nostalgia.25 Some have said that Dr. Rey (Arles) was brilliant and insightful. Their circular argument goes as follows: Rey embraced epilepsy without evidence of a full-fledged case; the commentators believe temporal lobe epilepsy (described many years later) is an attractive possibility; therefore they say Rey was ahead of his time. I join those who have judged Dr. Peyron as naive and trained in the wrong specialty, yet others have embraced as gospel his terse statements in the St. Re´my register. Tralbaut (1981) felt that the physicians of the south were overly influenced by the police reports in Arles, and by the patients own statements about a family history of epilepsy on his mothers side. If so, then the circle was indeed completed when Vincent wrote to Theo, as far as I can make out, the doctor here [Dr. Peyron] is inclined to consider what I have had [was] some sort of epileptic attack (letter 591). Theo van Gogh died in a mental institution in Den Dolder on January 25, 1891. Some of their medical records were released to Dutch newspapers in 1990, by a local archivist. The story, which covered the 38 days from Theos move out of Paris to Den Dolder until his death, ends dramatically, the final diagnosis was dementia paralytica [general paresis, a form of neurosyphilis]. At last the answer was out! Perhaps Vincent had the same thing?26 Dementia paralytica was described by Bayle, as early as 1822. Quincke is credited with introducing the lumbar puncture procedure together 23I have only one pleasant memory of this fiasco. While in Brisbane, Australia, as a guest for their van Gogh art exhibition in 1994, I was taken by a friend I have known since primary school to a beer garden. There he insisted on introducing me to everybody, eventually including a fellow in short pants and a singlet who was bouncing from table to table selling lottery tickets. Dr. Arnold is here for the big van Gogh affair, he is going to lecture tomorrow on van Goghs illness. We were both surprised by the smile of hidden wisdom and, I know mate, its Me´nie`res disease, my uncle had it. Alas, the misplaced power of immediate experience others have seen this in connection with manic depressive illness. 24The facts do not support the thesis (Arnold, 1995). However, it is even more bizarre to read that this sort of thing has been projected in some quarters as the crux of van Goghs underlying illness. 25In another setting the same group would supposedly be happy enough to acknowledge the laboratory developments that have advanced 20th century medicine. 26For reasons that still escape me the art politicians of Holland act as if the label of syphilis for the van Gogh brothers carries less social stigma than say alcoholism, let alone an inherited metabolic disease. Is this a misplaced attempt to protect the van Gogh family? THE ILLNESS OF VINCENT VAN GOGH 39 with examination of the cerebral spinal fluid for spirochetes, in 1892. Today, a definitive diagnosis would be based on serology of the cerebral spinal fluid, but this technology was not available until well into the twentieth century. General paresis was overly diagnosed in the nineteenth century. The psychiatric and neurological symptoms recorded from Theos case are far from definitive. An autopsy examination could have provided confirming evidence but apparently was not performed. In any event, the time course of Theos illness makes the case for neurosyphilis highly unlikely (Arnold, 1992). Dr. Paul Gachet also inherited his share of golden admiration. His ideas about Vincents illness are supposed to have included turpentine poisoning and the effects of too intense sun on a Nordic brain (Beer, 1935, p. 40). I have not been able to confirm the attribution to Dr. Gachet but I assume some verbal anecdote that slipped into the van Gogh literature. Vincent himself remarked upon being dazed with the sun (letter 512) that beats down on ones head . . . [and] makes one crazy (letter B15). Vincent may have been a bit reckless in his exposure but there was certainly more to his illness than heatstroke. The time course and the rest of the symptomatology cannot be accommodated under this heading.27 Rey, Peyron, and Gachet did their best to protect and rehabilitate the artist during those demanding two years. My observations within this section are not intended to disparage the van Gogh physicians but rather to make an appeal for placing their relative merits in perspective. They had the advantage of being there, but they were without benefit of the biochemical tools that we now take for granted. RESISTANCE FROM ART HISTORIANS, CURATORS, DEALERS, AND THE STATE MUSEUMS The art world harbors some people who deny any interest in van Goghs underlying illness. This position, albeit at odds with the public, takes various forms.Thus a catalog essaymay either skip over the subject or be content with he died by his own hand in 1890. During themonths of one blockbuster exhibition the museums education department managed to dodge a public lecture onVincentsmedical problems in favor of one recounting the provenance on the painting that fetched the best price at auction. Moreover, the vehemence with which so many art curators and dealers resist scientific enquiry suggests an unwholesome desire to maintain the mystique in order to protect the art.28 They do an injustice by assuming that the consumer of art needs protection. On the contrary, I believe that an explanation of Vincents underlying illness and the role of the environmentwill enhance rather than diminish genuine interest in van Goghs creations. The commercial interests of dealers and the ambitions of museums with regard to van Gogh foster the titillating connection between creativity and madness. Even if they are privately persuaded otherwise, they are reluctant to change something that they think is working. Newspaper and television journalists are reluctant to engage them on that turf and surely that is part of the reason for perpetuating the lengthy lists of possible van Gogh illnesses. They want to keep the subject vague in order to maintain the mythology. CONCLUDING REMARKS The house of Dr. Paul Gachet in Auvers-sur-Oise was recently opened to the public to coincide with 27I do not mean to defeat the message of this section but consider the following from an AIP expert, exposure to oil-based paints and solvents will, in some porphyrics, produce symptomatology including psychosis, colic, seizures, and neuropathy. Very rarely in acute porphyria, extreme exposure to sunlight may provoke an attack (Peters, 1986). Bonkovsky and I showed that pinene (turpentine) is porphyrogenic but sunlight! Was the good Doctor Gachet blessed? 28A curator at the Boston Museum of Fine arts once told me that he could not understand why anyone was interested in van Goghs illness. I ventured that at least it had something to do with his premature demise. No response, so I volunteered that Picasso and Matisse could have been contemporaries with Vincent if he had enjoyed a predicted lifespan of about 66 years how wonderful it would have been to have those three guys in the same room? Van Gogh painted lots of pictures anyway. 40 WILFRED NIELS ARNOLD the 150th anniversary of the birth of his most famous patient. Willem van Gogh, a greatgrandnephew of Vincent van Gogh, was in the crowd and he said he was touched to be present (New York Times, April 1, 2003). For those of us interested in round numbers it is also a propitious time to review the medical problems of the artist. A careful review of data from the artists letters and other contemporary sources indicates that Vincent suffered from an inherited disorder manifested by severe and manifold neurological problems, ranging from gastrointestinal pains to fits with hallucinations. His condition was exacerbated by his modus vivendi, which was marked by inadequate nutrition, abuse of alcoholic beverages, chronic smoking, environmental exposure, and the development of an abnormal affinity (pica) for terpenes. The intermittent nature of his illness, the sudden onset of crises, and the rapid return to normalcy after each episode, are all notable. The gamut of symptoms is best explained by a toxic psychosis. Within that category, the disease entity which most closely fits all of the data is acute intermittent porphyria [AIP], which was adopted by Loftus and Arnold (1991) and Arnold (1992) as a working hypothesis for Vincents underlying illness. This retrospective diagnosis has been compared and contrasted with other suggestions in the literature. The first case was described in a Dutch medical journal (Stokvis, 1889). AIP was not understood in Vincents time; even today it tends to be under-diagnosed. I am convinced that a toxic psychosis such as acute intermittent porphyria remains the best working hypothesis. Vincent van Gogh was not a mad artist, but rather an exceptional man who suffered from an inherited disease. He was wonderfully creative because of intelligence, talent, and hard work. He was a genius in spite of his illness not because of it. This reality enhances wholesome admiration for van Goghs creations. REFERENCES Andreasen NC (1987): Creativity and mental illness: prevalence rates in writers and their first-degree relatives. Amer J Psychiat 144: 12881292. Andreasen NC, Glick ID (1988): Bipolar affective disorder and creativity: implications and clinical management. Comp Psychiat 29: 207217. Arenberg IK, Countryman LF, Bernstein LH, Shambaugh GE (1990): Van Gogh had Me´nie`res disease and not epilepsy. JAMA 264: 491493. Arnold WN (1988): Vincent van Gogh and the thujone connection. JAMA 260: 3042304. Arnold WN (1989): Absinthe. Sci Am 260: 112117. 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Moore MR (1980): International review of drugs in acute porphyria. Int J Biochem 12: 10891097. Navratil L (1959): Vincent van Gogh: his disease assessed in the light of his paintings. CIBA Found Symp 7: 210216. Niedermeyer E (1983): Epilepsy Guide. Diagnosis and Treatment of Epileptic Seizure Disorders. Baltimore & Munich, Urban & Schwarzenberg. Penfield W, Jasper H (1954): Epilepsy and the Functional Anatomy of the Brain. Boston, Little, Brown and Co. Perry I (1947): Vincent van Goghs illness: a case record. Bull Hist Med 21: 146172. Peters HA (1986): Acute Hepatic Porphyria. In: Johnson RT, ed., Current Therapy in Neurologic Disease 1985-1986. New York, BC Decker, pp. 317321. Pickvance R (1984): Van Gogh in Arles. New York, Harry N. Abrams Inc. Pickvance R (1986): Van Gogh in Saint-Re´my and Auvers. New York, Harry N. Abrams Inc. Pinel P (1818): Nosographie Philosophique ou la Me´thode de lAnalyse Applique´e a la Me´dicine. Paris, Brosson, 6th edition. Prinzhorn H (1972): Artistry of the Mentally Ill (Translated by E von Brockdorff). New York, Heidelberg, Berlin, Springer-Verlag. (Original German version: Prinzhorn H. 1922. Bildnerei der Geisteskranken. Berlin: Verlag Julius Springer.) Rewald J (1986): Theo van Gogh as an art dealer. In: Gordon I, Weitzenhoffer F, eds., Studies in Postimpressionism. New York, Harry Abrams Inc, pp. 7115. Ridley A (1969): The neuropathy of acute intermittent porphyria. Quart J Med 38: 307333. Robbins SL (1957): Textbook of Pathology With Clinical Applications. Philadelphia & London, WB Saunders Co. Rothenberg A (1990): Creativity and Madness, New Findings and old Stereotypes. Baltimore and London, The Johns Hopkins University Press. Sarwer-FonerGJ (1988): The course ofmanic-depressive (bipolar) illness. In: Georgotas A, Cancro R, eds., Depression andMania.NewYork, Elsevier, chapter 4. 42 WILFRED NIELS ARNOLD Sassa S (1978): Toxic effects of lead, with particular reference to porphyrin and heme metabolism. In: De Matteis F, Aldridge WN, eds., Heme and Hemoproteins. Berlin, Springer-Verlag. Schmidt H (1915): lAbsinthe. lAlie´nation mentale et la criminalite´. Rapport fait au nom de la commission dhygie`ne publique de la chambre des de´pute´s. Annales dHygiene Publique et de Me´dicine Le´gale 23: 121133. SchnThe Illness of Vincent van Gogh Wilfred Niels Arnold Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KA, USA ABSTRACT Vincent van Gogh (18531890) was a wonderfully accomplished artist whose work is now widely appreciated. He created a great number of masterpiece paintings and drawings in just one decade devoted to art. His productivity is even more remarkable when considered in the context of his debilitating illness. He suffered from medical crises that were devastating, but in the intervening periods he was both lucid and creative. He left a profound, soul-searching description of his jagged life in his correspondence, which provides the basis for the present analysis. An inherited metabolic disease, acute intermittent porphyria, accounts for all of the signs and symptoms of van Goghs underlying illness. On this 150th anniversary of the birth of Vincent van Gogh it is appropriate to revisit the subject and to analyze the lack of organized skepticism in the popular media about other diagnoses. Keywords: Vincent van Gogh, inherited disease, acute intermittent porphyria, medical crises, absinthe, alcohol, thujone, camphor, pinene Vincent van Gogh was born in the presbytery of the Dutch Reformed Church of Zundert, in the southern region of The Netherlands, at 11:00 am on March 30, 1853. The obstetrician did not have far to run the office of Dr. Cornelis van Ginneken was right next door. There were no problems on that day. They would tumble out later. An eventful life was underway and it would last just thirty-seven years and four months. Today, van Gogh is on everybodys list of outstanding artists and in every catalog of creative people. He continues to find an appreciative audience of young and old, novice to connoisseur, all untrammeled by differences in cultural background or artistic education. It was not always so, at the time of his suicide in 1890 the accomplishments of Vincent were acknowledged by only a small cadre of friends and followers. No more than a handful of critics had put pen to paper. Formal recognition during his life was restricted to exchanges of paintings with other artists, gifts to friends and doctors, acceptance of canvases toward financial obligations, three sets of commissions, a drawing sold in The Hague, a few items sold in Paris, a selfportrait sold to a London dealer in 1888, and one sale from an influential Les Vingt exhibition (1890) in Brussels.1 He died still writing of hopes for future recognition, but indeed it was a deep disappointment for an artist who had been confident enough to follow the precedents of Michelangelo Buonarroti, Raphael Santi, and Journal of the History of the Neurosciences 2004, Vol. 13, No. 1, pp. 2243 Address correspondence to:Wilfred Niels Arnold, Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KA 66160-7421, USA. Tel.: þ1-913-588-7056. Fax: þ1-913-588-7440. E-mail: warnold@kumc.edu 1The sale of van Goghs artwork during his lifetime was obviously meager, but this list should replace the popular misunderstanding that Vincent sold only one painting. 10.1080/09647040490885475$16.00 # Taylor & Francis Ltd. Rembrandt van Rijn by using his first name alone for professional purposes.2 Posthumous praise for his creations roused attention but surely it has been the complementary interest in extraordinary aspects of the person, especially his underlying illness, that has made Vincent van Gogh a household name. His jagged life was marked by early years of uncertainty, interludes of luckless love affairs, wrenching episodes of self-mutilation, and crises of debilitating illness. Creative people who have shaken the world a bit are generally surrounded by popular contemplations about their physical and mental health. And in the visual arts the individual who makes the advance is all too often suspected of some individual abnormality, as if there were a need to invent an exotic explanation for the novelty. But in the case of van Gogh there were certainly enough unusual episodes to raise the question of mental derangement even during his lifetime. Given the extraordinary influence of the man on succeeding generations there are ample justifications for serious studies on whether medical problems affected his life or his artwork.3 THE PROBLEM Superficial interest and comment on van Goghs illness grew with every exhibition of his work. It became an industry with its own history. As a result, the typical newspaper article or exhibition essay declared that there were one hundred and one diagnoses on van Goghs illness!4 Six or seven examples were proffered, all embraced with equal weight by the reporter and without the benefit of a word of evaluation. Hopes of finding a better perspective in journal articles and books have not always been filled because the majority of the authors promoted pet ideas with selective inclusion of what they believed to be supporting data. I believe, axiomatically, that any reasonable working hypothesismust address all of the medical information; this includes family history and the artists lifestyle, as well as the underlying illness. The interaction between congenital disease and exacerbation factors is central to our argument. After Dr. Loretta Loftus and I published our working hypothesis of acute intermittent porphyria for Vincent and discussed the differential diagnosis (Loftus & Arnold, 1991) we were surprised to find that some critics, who did not offer any assessment of the facts we presented, were quick to respond with undocumented personal preferences in newspaper stories or letters-tothe- editor. Their epistles promoted alternatives that they claimed were more easily understood or more common disease entities, as if poor Vincent should become a poster-boy for the disease currently in vogue for creative people. Some made passing comparisons with other famous persons but usually without data on any of them. In some quarters the same weight was given to an opinion as to a well-referenced analysis. A large section of my subsequent book (Arnold, 1992) was devoted to van Goghs underlying illness. Therein I produced tables of Vincents own references (from his letters) organized by particular medical signs and symptoms, thus offering future scholars the benefit and convenience of a concordance. In the chapter Other Hypotheses I started with the assumption that all the authors were sincere but found that only a few advanced the field. It was also apparent tome that so many of those suggestions were loosely conceived and poorly documented, but they landed in the literature and in some cases had been widely quoted and requoted (errors to the third degree) without benefit of common sense. A blatant example is the silly claim of digitalis poisoning as a cause of van Goghs underlying illness. Art historians and others were quick to remark upon van Goghs occasional high yellow palette. This was hardly a revelation because the artist himself had written about his exaggerated use of yellow pigments and had coined the phrase. Vincents fondness for yellow can be gauged from his letters in the 18871890 period wherein he mentions the yellow of his surroundings more 2The paintings he signed (a small fraction of the total) were simply inscribed Vincent. I will use Vincent, van Gogh, and Vincent van Gogh interchangeably. 3Some commentators, mostly from the art history ranks, have denied the necessity to explore these questions. The possible reasons are analyzed later. 4I have encountered no more than a dozen serious proposals, but within each category there have been numerous renditions and rediscoveries. THE ILLNESS OF VINCENT VAN GOGH 23 than any other color (Arnold, 1992). But Lee (1981) was bold enough to propose that van Gogh suffered from a xanthopsia, wherein the patient has a reversible view of the world as if through a yellow filter, and that Vincent had been overexposed to digitalis, as a decoction of the foxglove plant. There is no doubt that too much digitalis will have this effect; the observation dates from the original dissertation (Withering, 1785); but there is no evidence that van Gogh ever took the drug, and artistic preference is still the best working hypothesis for the high yellow canvases (Arnold & Loftus, 1991). Also, and more important in the present context, it is absurd to include digitalis poisoning in lists of possibilities to explain all his neurologic and psychotic problems that culminated in suicide. The goal of the present review is fourfold: to evaluate our current understanding of van Goghs illness; to analyze some of the cultural and social aspects that impinge on (and interfere with) this field of van Gogh scholarship; to recommend a higher level of organized skepticism; and to promote the operational concept that the canons of proof associated with the hard sciences should also be applied to biography. THE IMPORTANCE OF THE LETTERS Theo van Gogh (18571891), who provided the emotional and financial supports for his brothers final decade, had realized the value of Vincents correspondence as a rich source of artistic and human interest. But he died the next year after Vincents suicide, and it took Theos widow, Johanna van Gogh-Bonger (18621925), another twenty-four years to decipher, translate, and arrange the letters before the first reasonable compilation appeared. In the preface, Johanna gave an additional reason, It would have been an injustice to Vincent to create interest in his personality ere the work to which he gave his life was recognized and appreciated as it deserved. (van Gogh-Bonger, 1978, xiii) The decision by Johanna van Gogh-Bonger to publish in English was based on her insightful anticipation of a world-wide audience for both Vincent the man and the huge amount of artwork that she inherited. She was well versed in the language and was also assisted in English phrasing and idiom by Helen Apel Johnson (Johnson, 1934). For many years the only edition of the letters that approached completeness was in English, and that had a profound effect upon the history of van Gogh scholarship. Vincents namesake nephew, V.W. van Gogh (18901978), identified as Vincent the Engineer, followed his mother in the activities of preserving the art work of his Uncle and organizing the copious correspondence, for which he anticipated the research potential by stating in his introduction that, the letters . . . are the only genuine source of details on his [Vincents] life (van Gogh, 1978, xi). During our 1990 conversation, Dr. Albert Lubin, professor of psychiatry and a van Gogh commentator (Lubin, 1972), made a special point about Vincents nephew being very much the amateur psychologist and a supporter of this type of enquiry. Unfortunately, in my opinion, Vincent the Engineer also endorsed some of the more mystical interpretations of the artists life.5 The three volumes of letters, memoirs, and editorial comments (van Gogh, 1978) are an important social, medical, cultural, and literary compilation. The descriptions of illness by the patient himself are central to our subject.6 In this review all references from The Complete Letters 5Dr. Humberto Nagera, another psychiatrist with direct contact, recently spoke to me about the Engineer being at odds with Paul-Louis Gachet (18731962), the son of Dr. Paul-Ferdinand Gachet (18281909). The father was Vincents last attending physician. Paul-Louis was a seventeen-year-old eyewitness commentator on Vincents final months in Auvers-sur-Oise, whereas the Engineer had to rely on information that was at best second-hand. One wonders whether the enmity of van Goghs nephew for young Gachet encouraged a splinter group that found fault with Dr. Gachets management of Vincents case and later criticized the whole Gachet family for exploitation of his art legacy. Their argument remains unconvincing and flies in the face of the generous donations (in 1949, 1951, and 1954) of van Gogh paintings to the state by Paul-Louis Gachet and his sister Marguerite (18691949). 6Most van Gogh commentators will not argue in public about the necessity of reading The Complete Letters, but it is no small undertaking (1,809 pages in all) and one may wonder how many have. 24 WILFRED NIELS ARNOLD will be noted, parenthetically, by letter numbers as they appear in the English edition of 1978. They overshadow the brief notes and register entries (Tralbaut, 1981) that have survived attending physicians in The Hague (unidentified hospital-doctors), Eindhoven (Dr. Van der Loo), Antwerp (Dr. Cavenaille), Paris (Drs. Rivet and Gruby), Arles (Drs. Rey and Urpar), St. Re´my (Dr. Peyron), and Auvers (Dr. Gachet). It seems inconceivable that Dr. Paul Gachet (18281909) kept no records, yet no journal or diary of patient visitations has been forthcoming from his office in the home at Auvers-sur-Oise.7 Biographical notes on all of the above physicians, as well as the influence of the home-remedies of Francois- Vincent Raspail (17941878), have been published (Arnold, 1992). MEDICAL SUMMARY Vincents ailment was characterized by episodes of acute mental derangement and disability which were separated by intervals of lucidity and creativity. Moreover, attending physicians, family, friends, and the artist himself were all surprised and encouraged by the rapidity of the recoveries after each crisis (van Gogh-Bonger, 1978). His serious illness developed late in the third decade, as evidenced by his concern with the possibility that [my] family might take steps to deprive me of the management of my affairs and put me under guardianship (letter 204). There was a family history of mental illness (Lubin, 1972; Tralbaut, 1981; Arnold, 1992). His underlying complaint was characterized by frequent gastrointestinal problems (letters 448, 530, B4, etc.), and at least one bout of constipation that required medical intervention (Tralbaut, 1981, pp. 177-8). The condition caused fits with hallucinations, both auditory and visual, (letters 592, W11, etc.) and evoked partial seizures (Tralbaut, 1981, p. 276). Periods of incapacitating depression and physical discomfort were severe and grave enough to provoke self-mutilation and eventual suicide (van Gogh-Bonger, 1978). Some of his bouts of sickness may have been associated with fever (letter 206) and sexual impotence (letter 506). His ailment was exacerbated by overwork (letter 173), malnutrition and fasting (letters 440, 571), environmental exposure (letter B15), excessive ingestion of alcoholic beverages (letter 581, etc.), especially absinthe (letter A16), and a proclivity for camphor and other terpenes (Arnold, 1988). The symptoms were palliated during institutionalization with better diet, alcohol restriction (letters 595, 599), and administration of bromide therapy (letter 574). In spite of their severity he did not experience any permanent, functional disability after any attack (Lubin, 1972; Tralbaut, 1981; Arnold, 1992). The reader is referred to Arnold (1992) for a much fuller treatment. In the paragraphs that follow I shall emphasize and explain specific aspects of van Goghs illness that are central to our working hypothesis and also dismissive of so many other hypotheses from the past. AGE OF ONSET In 1882, Vincent entered the city hospital at Brouwersgracht (a section of The Hague, in The Netherlands) with a gonorrheal infection, for an anticipated stay of no more than 14 days (letter 206). However, the hospital register (Tralbaut, 1981) indicated that Vincent was admitted June 7 and was not discharged until July 1 (a total of 25 days). To the surprise of his doctors, things took a turn for the worse after about 14 days, and Vincent complained by letter on June 22, of a dreadful weakness and wondered if there had been some complication that would make things worse (letter 208). He was moved to a new ward. The symptoms were only briefly described by Vincent but it extended his stay in the hospital for another 11 days. Was it a complication or a paroxysm? 7Son and daughter maintained the residence after the doctors death in 1909, and they were renowned for the care with which they preserved their fathers medical instruments and memorabilia. They had no children and were survived by distant relatives. Rumor has it that somewhere along the way all of Dr. Gachets records were intentionally destroyed to protect the privacy of his patients. His views survive only in the form of interesting anecdotes, and indirect reports with poor documentation of time or place. THE ILLNESS OF VINCENT VAN GOGH 25 There was a bizarre supplement. Van Gogh claimed that the attending physicians were willing to attest to his sanity (letter 206) if it were challenged again by his father. This statement is startling at first encounter but information taken from other letters indicates that his father had considered having him committed to an asylum in 1880 and again in 1881 (Arnold, 1992; letter 204; and letter 158 as amended by Hulsker, 1990). The hospitalization in The Hague took place when van Gogh was 29 years old. First indications of neuroses and psychoses occurred at age 27 (according to his fathers assessment). First expression of serious mental problems thus occurred late in the third decade of Vincents life. SIX MAJOR CRISES The last two years of van Goghs life included six well-documented medical crises with serious mental problems. The period under discussion, October 1888 to July 1890, is shown in Figure 1, which depicts calendar months (center line), sequential locations (bottom line), and the crises (stippled rectangles above the time line). Van Goghs suicide is marked with a Roman cross. The utility and power of the graphical presentation derive from the multiplicity of facts depicted and, in addition, from the visual summary (the Gesta¨lt). Thus we can see that the durations of the crises are variable (days, weeks, or months) and there is no discernible trend (the succeeding crises neither shorten nor lengthen in a regular manner). The five periods between major attacks show neither consistency nor trend. Their lengths were 38, 148, 116, 21, and 26 days. The range is large; the mean happens to be 70 days (standard deviation¼58 days). Vincent was a patient (voluntary inmate) at Saint Paul de Mausole Asylum at St. Re´my for just over a year (May 8, 1889 to May 16, 1890), although the initial plan had been for only three months. The attending physician, Dr. The´ophile Peyron (18271895), made occasional, spare notations in the register. Towards the end he wrote that the patient [van Gogh] . . . experienced during his stay in this institution several [medical] attacks with a duration of two weeks to a month. In reality, during the St. Re´my period with Dr. Peyron, the durations were 45, 7, 7, and 65 days in chronological order. The discrepancy suggests that Dr. Peyron was writing from memory, at some distance from the events. Van Gogh himself had not kept accurate records. In letter 631 Vincent wrote to brother Theo, I pointed out to [Dr. Peyron] that such attacks . . . have always been followed by three or four months [i.e. 90120 days] of complete quiet. I want to take advantage of this period to move [from St. Re´my to Auvers] The actual numbers were 70 58 days (see above). His last crisis at St. Re´my ended April 29, 1890. It is remarkable that a safe period of three months (Vincents intuitive but unsupported prediction) would literally terminate on July 29, 1890! The suicidal act (possibly inspired by an impending crisis) was committed on July 27. Each crisis had an abrupt onset and, at the end of days or weeks, a swift resolution. In some cases the artist even used words with the following implications one day fine the next day, down with sickness and yesterday I was too sick to write today I pick up the pen. It is worth Fig. 1. Time course of six major crises suffered by Vincent van Gogh. Details are given in the text. 26 WILFRED NIELS ARNOLD recalling how desperate the early prognosis about the December 1888 crisis had been. After Augustine Roulin (18521930) visited the hospital at Arles on the 27th, Vincent had increasing neurologic problems. The following day her husband Joseph Roulin (18411903) was unable to see him because van Gogh was suffering from aphasia. And then, on the last day of December, to the pleasant surprise of doctors and friends, the patient made a recovery so rapid and complete that Rev. Salles could report that he found him calm, in a state which revealed nothing abnormal (van Gogh-Bonger, 1978, xlvi). By the first week of January Vincent was moving around the hospital and conversing freely with Roulin and others, and even cautioning Theo not to alarm his mother and sister Wil. unduly (letter 569). On January 7, he returned to his home in Arles (made famous by his painting The Yellow House) and that day declared to his mother and sister that there is a chance that there will be nothing the matter with me for a long time to come (letter 569a). The periods between major attacks were remarkably normal. The lucidity with which the patient comprehended and wrote letters, discussed his condition with physicians, weighed the possibilities for the future, and maintained the quality of his art work, are all evident. From all indications (van Gogh, 1978; Tralbaut, 1981; Pickvance, 1984, 1986; Arnold, 1992), Vincent did not write letters and did not paint during crises. Unfortunately, this did not prevent future romantics (see for example Schnier, 1950; Navratil, 1959) from seeing disease in his art work! Potential precipitants of eight crises are summarized in Table 1; documentation will be provided later. The course of van Goghs illness is very instructive in approaching a retrospective diagnosis. The features are a guide to a working hypothesis that can then be either strengthened or challenged by further data. Hence any reasonable suggestion must first accommodate the kinetics and time course of van Goghs illness, and I would encourage organized skepticism in examining how poorly the observed data fit with ideas from the past. For example, we may ask whether a proposed medical entity usually presents with rapid (of the order of twenty-four hours) onsets and resolutions, or does the patient with the syndrome under discussion tend to drift through days or weeks into a debilitating episode and then later slowly emerge? Are the intervening periods marked by complete lucidity and impressive productivity or is there an indication of a cumulative neurological deficit and a mounting struggle to perform? Are the observed periods of Table 1. Precipitating Factors According to Arnold (1992). Date of crisis Location Precipitants 1880 The Borinage (Belgium) Fasting or general neglect of nutrition are possibilitiesa June 1882 The Hague (Holland) Gonorrheal infectionb December 1888 Arles (France) Alcohol (especially absinthe) February 1889 Arles (France) Camphor, fasting, alcohol (especially absinthe) JulyAugust 1889 St. Re´my (France) Alcohol (especially absinthe) consumed in Arles during a social visit December 1889 St. Re´my (France) Exposure to turpentinec January 1890 St. Re´my (France) Alcohol (especially absinthe) consumed in Arles during a social visit FebruaryApril 1890 St. Re´my (France) Alcohol (especially absinthe) consumed in Arles during a social visit. This crisis actually started in Arles Note. aPoorly documented, but related to the concerns of van Goghs father. bWe refer to the complication that followed the primary infection. cExpression of a pica (Arnold, 1988) for terpenes and terpenoid compounds: camphor, pinene (in turpentine), thujone etc. from absinthe. THE ILLNESS OF VINCENT VAN GOGH 27 pronounced illness for van Gogh compatible with a candidate disease, or would one expect minutes or hours months or years? With any of these other proposals, would attacks be precipitated by seemingly unrelated factors such as fasting, microbial infection or xenobiotics? All the while we must bear in mind that Vincents organized care during the medical crises of the last two years was practically limited to bed rest, one prescribed drug (potassium bromide), good nutrition, and restriction of alcoholic beverages. During van Goghs hospitalizations the attending doctors, nuns, and other attendants were essentially engaged in sympathetic nursing and patient-protection, in response to observation and concern. THE ROLE OF ABSINTHE Artists painted and poets personified; men and women embraced the ritual of presentation as well as the appearance, taste, and excitement of the liqueur called absinthe. Some of the most creative people of the nineteenth century were included. The aesthetics of absinthe drinking contributed to its popularity. Nevertheless, one looks beyond ethanol to the mood-altering chemicals that were unique to this alcoholic beverage in order to rationalize the volumes consumed in some quarters (Arnold, 1989). There was a fifteen- fold per capita increase in France from 1875 to 1913, when the national annual consumption attained a massive 9.7 million U.S. gallons. Whenever you have this many people imbibing a particular beverage, there must be more to it than poetry and attractive colors. In the department of Bouches-du-RhoË?ne, which includes van Goghs southern venues of Arles and St. Re´my, the annual consumption was an impressive 2.45 liters per head, which was more than four times the national average (Schmidt, 1915). VINCENT VAN GOGH AND THE INDIVIDUAL RESPONSE Some years ago, while perusing the letters of Vincent van Gogh, I was intrigued by the chemical connection between absinthe constituents (such as the toxic compound called thujone) and some other terpenoid compounds in his life. These exposures involved Vincents use of massive amounts of camphor to combat insomnia, an attempt to drink essence of turpentine (pinene), and references to his nibbling at oil colors (mixed with turpentine). The possibility of an interaction became more compelling when I read Sollmann (1948) on thujone and camphor, wherein he remarked that the convulsions induced in experimental animals are antagonized by bromide, while the threshold is lowered by nicotine. While institutionalized in Arles, van Goghs crises were ameliorated by taking bromides and decreasing smoking. Accordingly I suggested that van Gogh had developed an affinity or a pica for terpenes, the documented examples being thujone, camphor, and pinene (Arnold, 1988).8 This would help to explain some of the strangest of van Goghs acts during his last two years his attempts to eat his paints and to drink turpentine and kerosene which were previously regarded as absurdities and unrelated. The response to any drug or xenobiotic depends upon a variety of factors not least of which the nutritional status of the subject. For example, an increased toxicity of camphor and related compounds is noted during fasting and is attributed to a compromise in glucuronic acid formation (Sollmann, 1948).9 Infections and unerlying illness also play critical roles in determining the individuals response to drugs. There are several indications in his letters and in painted objects that Vincent developed an affinity for absinthe. He painted The Night Cafe on the spot, staying up three nights in a row and sleeping during the day (letter 533). It is tempting to speculate that he had a glass or two during the execution of this painting; he certainly had access, and the landlord was apparently pleased with the whole event. Apart from the 8Pica comes from the Latin for magpie, a bird who carries away odd objects. In medical terminology it refers to compulsive eating of non-nutritive substances and has been ascribed to various disorders including malnutrition. 9Camphor is secreted in the urine as hydroxycamphor glucuronide. 28 WILFRED NIELS ARNOLD possibility of this special case, we do not imply that van Gogh painted while intoxicated. There has been much discussion on the amount of absinthe (and other alcoholic beverages) consumed by Vincent in Paris, Arles, St. Re´my, and Auvers. At one extreme we have Jan Hulsker who steadfastly maintained that Vincent was not a drinker (Hulsker, 1990). In an earlier publication (Arnold, 1988) I described a pastel by Toulouse- Lautrec and mentioned that it depicts Vincent partaking of a glass of absinthe. Hulsker (1990, pp. 401404) objected to partaking and insisted on the static message that Vincent only sits before the glass. That Toulouse-Lautrec chose to depict Vincent with a glass of absinthe suggests to me that it was a common enough circumstance, and that Vincent drank absinthe. We feel that van Gogh was not in the habit of simply decorating his table with a glass of absinthe in front of him as Hulsker would have it (Hulsker, 1990, p. 322). That commentator maintains the isolated position that there is no evidence that van Gogh was fond of absinthe, and he also denies all the statements and anecdotes about his drinking problem. Alas, Hulsker defeats his own hypothesis in several places, not least of which when he suggests that Vincents lack of recall of the ear-cutting episode was because drinking had caused him to black out (Hulsker, 1990, p. 322). At the other extreme we have those reporters with a list who would include absinthe abuse as a free-standing explanation for all of Vincents problems. Other commentators, who had been told that their initial hypotheses didnt accommodate all of van Goghs signs and symptoms, subsequently invoked absinthe as a rider. I provided a concordance on Vincents references to alcohol, including letters in which he expressed fear of becoming an alcoholic (Arnold, 1992, p. 79). Paul Gauguin (18481903) lived with van Gogh during the two months running up to Vincents first crisis in Arles. Anecdotes suggest that Gauguin consumed at least as much absinthe as van Gogh, but he did not exhibit the same medical problems. If so many were drinking absinthe, why did his neighbors (letter 579) regard Vincents behavior as so bizarre? The explanation that has escaped most reviewers is that Vincent was abnormally sensitive to absinthe, even in the amounts associated with social drinking, because of his congenital illness. Absinthe is but one factor in the environmental impact on Vincents underlying illness; it also comes under the category of lifestyle. Hemphill (1961) deserves much credit for being the first to consider absinthe as an external chemical influence on van Gogh. Vincent himself seemed to be approaching this idea when he wrote, it seemed to be caused more by some outside influence than by something within myself (letter 605). Loftus and Arnold are convinced that it was the underlying illness of acute intermittent porphyria that made Vincent so sensitive to absinthe and malnutrition. ACUTE INTERMITTENT PORPHYRIA (AIP)10 AIP is one member of a class of metabolic abnormalities, the porphyrias, which are characterized by the excessive production of porphyrins, or related compounds (Waldenstro¨m, 1957; Kappas et al., 1989). Individuals who suffer from these diseases are prone to excrete elevated concentrations of these same compounds in their urine and feces. The abnormal excretion per se is of no intrinsic medical import but it is a reflection of elevated concentrations circulating within the body, and therein lies the potential for cutaneous photosensitivity (due to porphyrins), neurological abnormalities (due to porphyrin precursors), or both. In the case of AIP, all of the symptoms are neurological and the specific, overly-produced compounds are d-aminolevulinic acid and porphobilinogen. These are intermediates in the metabolic pathway to porphyrins, which in turn are used in the biosynthesis of the heme of hemoglobin, and other heme-containing proteins. Acute refers to the rapid onset, and abrupt cessation, of expressed symptoms. (The underlying cause of AIP is present from birth, so in that sense it is chronic.) 10Please consult my book (Arnold, 1992) for a much fuller discussion of acute intermittent porphyria. Only the most salient primary references will be given here. THE ILLNESS OF VINCENT VAN GOGH 29 Intermittent refers to the periodicity, which is typical, and emphasizes the distinct periods of normalcy which intercede between the episodes of illness. Symptoms rarely occur before puberty; the peak decade for onset of symptoms is from age 20 to 29 (somewhat later for males than females) but the disease sometimes remains latent throughout a lifetime (Waldenstro¨m, 1957). Tabulations of the most common hallmarks emphasize abdominal pain and other gastrointestinal complaints, symptoms referable to the peripheral and central nervous systems, and signs of autonomic neuropathy including tachycardia and hypertension. Porphyria-induced hypertension can cause early-onset renal failure (Laiwah et al., 1983). Bladder dysfunction may result in urinary retention (Laiwah et al., 1983; Kappas et al., 1989). Effects on optic nerves or the occipital lobes have been documented for AIP cases (Ridley, 1969). Sexual impotence (Kappas et al., 1989) has occasionally been reported. Premonitory symptoms include restlessness and irritability; attacks develop rapidly; resolution may occur in days or sometimes weeks, in an unpredictable fashion. Seizures do not always attend severe crises, but when they domany antiseizure drugs, with the notable exception of bromides, may adversely affect the outcome (Bonkovsky et al., 1980; Moore, 1980). The unpredictable nature of the disease with respect to both onset of crises and outcome makes an acute attack of AIP particularly treacherous. It can be one of the most terrifying experiences imaginable. Patients can become almost completely paralyzed in severe cases. They are unable to breathe, swallow or communicate properly, yet remain conscious for some time, all the while suffering pain, being aware of their plight, and wondering if it will ever end. The most common cause of death from AIP is respiratory paralysis. Most importantly, the expression of neurological and other symptoms depends upon lifestyle and exposure to precipitating factors. Early examples of AIP were revealed as a response to new drugs; initially the hypnotic Sulfonal (2,2-bis (ethyl sulfonyl) propane), later barbiturates; and subsequently many other drugs, alcohol, and sundry organic compounds (Moore, 1980). Some steroid metabolites precipitate attacks, and endogenous changes may account for some crises at puberty and the earlier onset with females. Other exacerbating factors include infections and malnutrition (Kappas et al., 1989). Low-carbohydrate and low-protein diets are especially detrimental (Welland et al., 1964) and fasting can precipitate an attack of porphyria (Knudsen et al., 1967). A study in Scotland indicated an association between smoking (nicotine is metabolized via cytochrome P450) and the induction of repeated attacks in patients already diagnosed with AIP (Lip et al., 1991). Even an excess of coffee may be a problem because caffeine is also porphyrogenic (Moore, 1980). VINCENT VAN GOGH AND AIP All of the hallmarks of Vincents illness can be accommodated within this overview of AIP. The most important and well documented are the gastrointestinal complaints, neurological disturbances, age of onset, jagged time course, and the exacerbations caused by inadequate nutrition and absinthe abuse. Other aspects such as sore throats, eye problems, fevers, a bout of aphasia in the Arles hospital, and impotence, have other possible causes but are all compatible with underlying AIP. Van Goghs smoking habit may have contributed to recurrent attacks. Vincents urinary tract infection in The Hague may have precipitated an AIP crisis leading to the complication and extended hospitalization at that time. It is also possible that his urinary retention recorded at that time was exacerbated by an AIP attack. Arnold (1988) suggested that van Goghs fondness for absinthe developed into a pica for terpenes, the documented examples being thujone, camphor, and pinene. It is worth noting that 1,8 cineole, a constituent of crude camphor and wormwood oils, is a proven precipitating agent for AIP (Bickers et al., 1975). Van Gogh used reckless doses of camphor oil against insomnia (letter 570) and absinthe contained a variety of essential oils including wormwood. Bonkovsky and Arnold have shown that camphor, thujone, and pinene are porphyrogenic (Bonkovsky et al., 1992). The combination of overexposure to camphor, absinthe abuse, and fasting or 30 WILFRED NIELS ARNOLD malnutrition would be injurious for anyone, but devastating for someone with AIP. Loftus and Arnold (1991) believe that all recorded signs and symptoms of Vincents illness can be accommodated by acute intermittent porphyria. Arnold (1992) presented cases of AIP from the 20th century that had analogies to the illnesses of Vincent, Theo, and their sister Wil. (1862 1941). It behooves proponents of other hypotheses to provide similar case histories, complemented with the diagnostic insights ofmodernmedicine, to either support or damage their alternatives. THE BIOCHEMICAL LESION IN AIP Almost any cell in the human body can engage in synthesis of heme because it is not only vital to hemoglobin but also for the cytochromes involved in so many aspects of metabolism. The biochemical pathway to heme consists of eight enzymes and an exquisite control mechanism. A partial deficiency (about half of normal) of enzyme (catalyst) number three (porphobilinogen deaminase) in this sequence is the underlying cause for the manifold derangements of the AIP patient under crisis. The organ of primary concern for this inherited disease is the liver, where two thirds of the heme that is produced is incorporated into the various types of cytochrome P450. An even larger proportion attains during the induction of P450s, which attends the livers encounter with xenobiotics. The AIP patient has a vulnerable heme pathway. The neurological problems associated with medical attacks are a consequence of upsetment of the heme pathway and the toxic accumulation of two intermediate compounds, daminolevulinc acid (ALA) and porphobilinogen. Because porphobilinogen deaminase is not ratelimiting to the overall pathway, 50% of normal is sufficient for unstressed AIP patients. This explains the lack of symptoms for latent AIP patients and the intervening periods of normalcy for patients who have experienced periods of sickness. It is the first enzyme in the pathway, ALA synthetase, that is normally rate-limiting. Therein lies the major control feature because heme (the end product of the pathway) causes both a repression and an inhibition of ALA synthetase. When the heme concentration of liver cells is depleted, the effective amount of ALA synthetase may be increased over ten-fold. Under those circumstances the partial road block at enzyme number three for AIP patients is felt, and toxic levels of the preceding compounds are produced. Ingested compounds that are metabolized via cytochrome P450s in the liver deplete the heme pool and induce the synthesis of ALA synthetase. These include alcohol, many drugs, and many xenobiotics (Moore, 1980). The van Gogh terpenes (camphor, thujone and pinene) can be added to that growing list (Bonkovsky et al., 1992). On the other hand, synthesis of ALA synthetase can be decreased by high glucose intake, thus helping to explain the ameliorating effect of a high carbohydrate diet on AIP attacks and the adverse effect of malnutrition or fasting (Kappas et al., 1989). More extensive discussions of the heme pathway are given elsewhere (Kappas et al., 1989; Arnold, 1992) and further pursuit of the biochemistry is not appropriate to this review. However, I would like to offer an hydraulic model of the control mechanism to assist the non-chemical reader. The diagram on the left of Figure 2 represents each intermediate compound (a,b,c . . . heme) as a solution in a cylinder being acted upon by an enzyme (exit tube) as it passes on to the next vessel. The AIP patient has about half the normal amount of the third enzyme (exit partly closed by the bold arrow). But the overall flow is steady thanks to regulation of the first enzyme (the float mechanism senses the level of the heme pool). The diagram on the right depicts the consequence of depleting the heme pool (pulling the plug): the activity of the first enzyme increases greatly (increased drop-size in the model) and now the partial block at the third enzyme (in the AIP patient) comes into play. Compounds c and d accumulate and will spill-out (X). Only under a crisis does the AIP patient excrete large amounts of d-aminolevulinic acid (compound c) and porphobilinogen (compound d) in the urine. Even then the freshly voided urine is of normal color, but with time these compounds polymerize to form porphobilin which imparts a brown or red (the color of porphyry) pigmentation to aged specimens. The final color is influenced by concentration, pH, light, oxygen and temperature. THE ILLNESS OF VINCENT VAN GOGH 31 The propitious availability of a porphyric urine sample together with the low-tech windowsill test can be very instructive in the diagnosis of AIP. Urine which has aged internally due to bladder dysfunction may already be discolored when released with a catheter, although the color is sometimes mistaken for urinary tract bleeding. In contradistinction to the claim that port wine urine is the faithful telltale sign of AIP, it is worth emphasizing that many 20th century carriers with documented medical attacks have never remarked upon abnormally colored urine because it was either not saved or not aged. Dark or red urine is not mentioned in the published van Gogh letters but this really does no damage to the AIP hypothesis.11 Barker and Estes (1912) were the first to note that AIP runs in families. The extensive studies of Waldenstro¨m (1937) in Sweden firmly established the inherited nature of the disease. The disease follows an autosomal dominant pattern of inheritance; if one parent is a carrier then on the average 50% of the children will bear the defective gene (Kappas et al., 1989). However, the penetrance is variable, so that in some families only a fraction of the carriers actually express signs and symptoms of the disease (Gates, 1946). Vincents mother died at 88, having led a seemingly healthy life. His father, the Reverend Theodorus van Gogh, died at 63; his studies for the church had been interrupted by serious illness; he was judged not to have been in very good health most of his life (Tralbaut, 1981). It is believed that he died from a stroke and, because hypertension is present in over half of AIP patients (Goldberg, 1985), this underlying disease would be one of many possibilities compatible with that cause of death. Of Vincents parents the father may be the more likely (obligate) carrier of AIP, but this is little more than an educated guess. He led a careful and balanced life in his post in the wilderness (Tralbaut, 1981) and may have avoided the Fig. 2. An hydraulic model for the control mechanism in the heme pathway. Details are given in the text. 11Critics of the AIP hypothesis for Vincent have occasionally pretended that this was a serious deficiency. It is negative evidence at best but can be rationalized. Vincents accommodations were often primitive by todays standards; for example, the Yellow House in Arles had no toilet and he used the facilities at the hotel next door (letter 480). He relieved himself in the field while painting. Moreover, even if he encountered reddish urine he may well have attributed it to blood, given his experiences with catheters and bougies at The Hague (letter 209). 32 WILFRED NIELS ARNOLD precipitating factors that affected three of his six children. There were numerous exchanges between the brothers concerning their nervous problems. It is not clear whether Theos serious illness at age 19 was related to the expression of AIP-like symptoms, but certainly by December 1886 (age 29) according to his future brother-in-law, Andries Bonger, he had serious nervous complaints, so bad that he could not move (Hulsker, 1990, p. 455). Theo seems to have been in reasonable health at the time of Vincents funeral. But two months thereafter Theo suffered further leg pains and also hallucinations (partly in response to an unspecified medicament for his cough), became very irritable and occasionally violent, muttered with difficulty in mixed languages, experienced urine retention, and was totally unconscious with a barely detected pulse before he died (aged 34) (Rewald, 1986, p. 69; Hulsker, 1990, p. 455). Leg pains, mental illness, and paralysis would all support a diagnosis of AIP, and the violent reaction to a new drug and renal failure would be in accord with AIP (Arnold, 1992). On the other hand the reversibility of the leg pains does not support the diagnosis of neurosyphilis offered by Dr. Frederik van Eeden.12 Vincents youngest sister, Wil., spent the latter half of her 79 years in an asylum for psychiatric cases. She may also have suffered from AIP, although the lack of further documentation makes her case much more speculative. The youngest brother, Cor, died at 33 in South Africa from an accident while feverish; it may have been a suicide. Again, the medical history is scant. His other sisters, Elizabeth and Anna, lived 77 and 75 years respectively, without any indication of medical crises (Arnold, 1992). Loftus and Arnold (1991) and Arnold (1992) discussed the differential diagnosis of Vincent van Gogh in favor of acute intermittent porphyria. We hoped that the facts would speak for themselves and that informed readers would have no difficulty in rejecting other hypotheses.13 In the decade that followed there was no new hypothesis, but we encountered ongoing competition from several old ones, whose authors were occasionally quite vocal via the popular media. It is beyond the scope of this review to look back on more than a selection of these. VINCENT AND EPILEPSY? Epilepsy is defined as a paroxysmal (sudden and recurring) transient disturbance in brain function that is manifested by episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. The derivation of the word is Greek; it means seizure. Accordingly, the term epileptic seizures is redundant, but common parlance. Another basic term is convulsion, which means a violent involuntary contraction, or series of contractions, of the normally voluntary muscles. Niedermeyer (1983) emphasized that epilepsy is not a disease but rather an abnormal reaction of the brain due to numerous causes. Several diseases and conditions are complicated by seizures and convulsions. They may accompany withdrawal from alcohol or barbiturates and attend uremia. Other acute illnesses which present with seizures include hyponatremia, thyrotoxicosis, the acute porphyrias, and hypoglycemia. Lead and arsenic are the most frequently encountered metallic intoxications which cause convulsions. Tonic-clonic convulsions were not described by Vincent or his doctors, so grand mal seizures have never received much diagnostic support. Petit mal or absence seizures (a brief lapse in 12Theo died at Willem Arntsz Stichting, near Utrecht, on January 25, 1891. The local diagnosis was neurosyphilis. This item was discovered 100 years later by Dr. A. Pietersma, Archief Dienst Gemeente, Utrecht. 13Informed readers turned out to be a bigger assumption than anticipated. A fatuous example came from an East-Coast psychiatrist who wondered if the subsequent lack of reference to our work is related to it being published in The British Medical Journal, a journal that is not widely read in the U.S. and your main thesis being published in a monograph (private correspondence). THE ILLNESS OF VINCENT VAN GOGH 33 consciousness usually no longer than twenty seconds) are certainly not indicated. Thus the classical sorts of epilepsy, which were well understood in Vincents time, were hardly indicated. For this reason I agree with Tralbaut (1981) that Dr. Peyrons unqualified diagnosis of epilepsy in the St. Re´my register was based upon the patients preconceived, ill-informed view.14 If indeed Drs. Rey and Urpar (Arles), and Peyron (St. Re´my) were convinced that Vincent van Gogh had some sort of epilepsy, then why wasnt he treated for it?15 Admittedly the available therapy was meager, but Vincent was not even treated symptomatically at St. Re´my, and no advice along those lines was passed on to Paris when Vincent departed. Contrast Vincents casewith that of Fyodor Dostoevsky (18211881) who wrote, on June 17, 1863, I go to Paris and Berlin . . . only for consultation of specialists (Trousseau in Paris, Romberg in Berlin) for my epilepsy (Voskuil, 1983, p. 665). If they really thought he had epilepsy, it is curious indeed that Vincent, a quarter of a century later, was not referred to an epilepsy specialist at Montpellier or Paris! As early as the 1870s, Hughlings Jackson had described certain hallucinations with seizures that he related to a pathologic condition of the temporal lobe (Jackson, 1931). Later, so-called psychomotor seizures were well described (Gibbs et al., 1937). In the 1950s the anatomical adjective temporal lobe was again preferred, even though some other parts of the brain were sometimes involved (Penfield & Jasper, 1954). Today, these are all lumped under complex partial seizures (Gastaut, 1970). Dr. Edgar Leroy, who worked at St. Re´my Asylum, albeit many years after van Goghs sojourn, and Dr. Victor Doiteau considered that Vincent was epileptic but found no evidence of aura or frank convulsions and suggested temporal lobe epilepsy (Doiteau & Leroy, 1928). See also Vinchon (1960). A diagnosis of temporal lobe epilepsy might explain Vincents hallucinations, the episodic nature of his illness, and the interictal periods of normalcy. However, the usual duration of minutes or hours that attends the various forms of complex partial seizures does not fit the days and weeks of Vincents crises. More importantly, epilepsy does not accommodate the numerous gastrointestinal complaints. Likewise, some of the factors which exacerbated his illness such as malnutrition and fasting are not noted for inducing temporal lobe epilepsy. Drug therapy in the 1880s was limited, but Vincents fits and confusion (letter W11) seem to have been controlled in Arles by bromide (letter 574), which would be indicated for absinthe intoxication or acute intermittent porphyria, but not for temporal lobe epilepsy. Bromides are effective against grand mal and simple partial seizures but not for complex partial seizures (Hemphill, 1961; Niedermeyer, 1983). Monroe (1978, 1992) noted that the limbic system is exquisitely sensitive to stress and external toxins including alcohol, and he remarked on Vincents affinity for absinthe. This was rediscovered by Blumer (2002), who was adroit in avoiding all the data on van Gogh that did not fit temporal lobe epilepsy. MANIC-DEPRESSIVE ILLNESS (BIPOLAR AFFECTIVE DISORDER)? The assumption made by some commentators that manic-depressive psychosis was unknown in Vincents day is incorrect. Falret (1854) had described so-called circular insanity in which mania and melancholia alternated at regular intervals. Note that the term melancholia was still used, but the meaning was by then approaching a modern definition of depression.16 The same 14Tralbaut felt that the doctors at Arles and St. Re´my were sympathetic to van Goghs suffering but not particularly interested in taking a complete medical history. My impression is that they were completely baffled by Vincents illness. 15Claims (Gastaut, 1956) that Felix Rey (a young intern still in training) was ahead of his time, and that his friend Aussoliel was a local expert on masked epilepsy, are not convincing. 16The first good description of a relationship between mania and melancholia came from the Englishman ThomasWillis (16211675), who mentioned that one can change into the other . . . this cyclic disorder is like a burning object, one that can produce smoke or flame (Willis, 1672; Finger, 2000). 34 WILFRED NIELS ARNOLD year, Baillarger (1854) also wrote about these two states, and also included an intercalated period of normalcy as an integral part of the syndrome. It should be mentioned in passing that Dr. Paul Gachet attended lectures by both Falret and Baillarger.17 A protracted dispute over priority ensued, although it would seem that Baillargers double-form disease was closer to our present concept (Kra¨pelin, 1921) of manic-depressive psychosis or bipolar disorder. The French Academy of Medicine had major meetings on the subject starting in 1880. How well it was recognized, received, or dealt with in Arles and St. Re´my in 1889 and 1890 is an open question, especially as to the intent of Drs. Urpar and Peyron when they used the term acute mania. I am inclined to think that they were referring to the December 1888 events in and around the earcutting incident and Vincents first hospitalization, and then the complaints of neighbors about Vincents drinking sprees which led to his readmission to the Arles hospital in 1889. If that is true then it was old fashioned mania a la Pinel.18 By 1900 mania had assumed its present psychiatric meaning of a mood disorder characterized by expansiveness, elation, agitation, hyperexcitability, hyperactivity, and increased speed of thought and speech (flight of ideas). Up until the beginning of the 19th century, the prime meaning of melancholia was intensity of idea, the image of the mind being strongly fixed on, and frequently returning to, a single set of ideas, to an extent that was deemed unhealthy. The connotation of sadness was not always present, and many forms of behavior that have little relationship (from our perspective) were included in the general class of melancholia. Not surprisingly there was even a productive melancholia that today might be more akin to intense, creative, concentrated thinking directed at a particular problem, while excluding all day-to-day distractions (monomania). Thus melancholia moved through monomania to depression and it is difficult to gauge how far Dr. Peyron had progressed.19 Perry was probably the first to discuss manicdepressive psychosis as a diagnosis for Vincent van Gogh; her expression was cyclothymic personality with episodes of depression and mania (Perry, 1947, p. 171). In the opinion of Hemphill, van Gogh was a manic-depressive who developed confusional episodes and fits in the last two years of his life due to the toxic action of thujone, the active agent of absinthe (Hemphill, 1961, p. 1084). Hemphills contribution was twofold; he was the first to correctly refer to Vincents epilepsy as a disorder rather than a disease, and he stressed the evidence for a toxic psychosis. He supposed that the gastrointestinal complaints came from the absinthe abuse alone, whereas Arnold and Loftus stress van Goghs sensitivity to absinthe (and other xenobiotics) due to the underlying disease of acute intermittent porphyria. Other writers have marched Vincent down the bipolar trail but have discovered nothing new since Hemphill (1961). Manic depressive illness is widely diagnosed today and a significant part of the pharmaceutical industry is devoted to discovering further chemical assists for the sufferers. These patients are rarely aware of their states and ordinarily do not check themselves into hospitals. Their disorders do not have acute onsets and offsets and the time course of van Goghs illness certainly does not fit that syndrome. However, it is common enough for artists and museum patrons to know, or think they know, something about the syndrome and someone in their immediate circle who has it. Proponents of this working hypothesis exploit this statistical swell even though they should be arguing about the illness of just a single individual, Vincent van Gogh. 17The title of Dr. Gachets thesis was E ´ tude sur la Me´lancolie (Gachet, 1858). The work was written in 1858, in the middle of this transition period in terminology. His thesis was really a compendium of principles for moral treatment of the insane, spiced with a philosophical vitalism that he encountered at the Montpellier Medical School (Fabbri, 1966). 18In Pinels book (1818), mania was a disorder of one or more faculties with sad, gay, extravagant or raging affect, but always included blind aggression. 19The´ophile Peyron (18271895) made his first medical career in the navy and then settled in Marseille as an oculist. His appointment as director at the asylum of St. Re´my may have been a semi-retirement position, as Vincent hinted (letter 593). THE ILLNESS OF VINCENT VAN GOGH 35 A course of regular cycling between mania and depression, which is popularly held, is rarely observed (Sarwer-Foner, 1966). On the average there are nine to ten depressive episodes for every manic event. A histogram of overall frequency versus age-of-onset for manic-depressive patients [n¼898] peaked with the 1519 year group, and was closely followed by the 2024 year group (Goodwin & Jamison, 1990). Notwithstanding considerable searching, biochemical and genetic markers for bipolar affective disorder have yet to be found. It has been widely observed that many creative people had illnesses that were serious, debilitating, and sometimes limiting to their productivity. The majority opinion is that these men and women were successful in spite of illness, and not because of it. It is also true that many creative people enjoyed robust and healthy lives.20 During the 18th and 19th centuries there lived an unfortunate philosophy relating the fevers of tuberculosis to activities on a higher plane. This romantic notion has now fallen by the wayside, but during the last twenty-five years manic depressive psychosis has popped up and down as a fashionable disease of association with creativity. Andreasen (1987) evaluated 30 faculty members, over a 15-year period, at an American university workshop for creative writing. She claimed that the writers had a substantially higher rate of mental illness compared with 30 control subjects matched on sociodemographic grounds. A higher rate of affective disorders, especially manic depressive psychosis, was reported for the so-called creative group as well as their firstdegree relatives. Jamison (1989) reported that 38% of a British group consisting of 39 writers and 8 artists, which she deemed outstanding, had sought treatment for some form of affective disorder, especially manic depressive psychosis, compared with lifetime prevalence rates in that nation of about 6%. Her attempts to link hypomanic episodes and seasonal mood swings with productivity were unconvincing. Rothenberg (1990) criticized both the Adreasen study and the Jamison follow-up on the grounds that little consideration was given to the subjects reasons for participating in the studies, and the criteria for judging them creative were left unexplained. Furthermore, Andreasons self-reliance on evaluation of relative mental health was potentially biased because the subjects and controls were already known to her. And Jamison built her case on the subjects own reports of seeking medical treatment. Goodwin and Jamison (1990) came up with a list of people they judged to have been creative together with an indication (opinion) that they suffered from manic depressive illness. The cautious message from all of this should be that such a debilitating condition is still compatible with creativity, but in some circles there has been an inference of causality.21 For example, Jamisons book on manic depressive illness and the artistic temperament (Jamison, 1993) certainly leaves the reader with the indication that the creative are more susceptible to manic depressive illness than the normal run of people, and the impression that a sort of Faustian bargain is at play. SCHIZOPHRENIA? Progressive changes in content and style have been observed in the work of artists who are deemed to have schizophrenia (Prinzhorn, 1972). The reverse namely to see the psychosis in unknown artists by looking at their work is obviously more difficult, but not sufficiently daunting to inhibit the proponents of schizophrenia for Vincent van Gogh. Such was the approach of Jaspers (1922), who is still quoted under this heading. Vincent had hallucinations, and he also had at least one episode of paranoia when he thought that neighbors were trying to poison him in Arles, but these are not specific for schizophrenia. The progressive deterioration of the untreated 20There have been some futile attempts at constructing ratios. My friend Don Goodwin accused them of playing a floating game as they found more candidates to be healthy they would add others to the numerator by sticking them with illness labels. 21There is also some overlap here with Dr. Gachets thesis list of outstanding individuals who suffered from melancholia (Gachet, 1858, pp. 922). 36 WILFRED NIELS ARNOLD schizophrenic is lacking in van Gogh. Perry remarked that [Vincent] did notwithdraw from the world; he was cast out because of his behavior (Perry, 1947, p. 162). The schizophrenic has a decrease in affect whereas Vincents letters and pictures were surcharged with emotion. Hemphill (1961) saw no sign of schizophrenia in the artist and emphasized that there was never any fantasy formation, and that his letters were lucid and logical. There is no case for schizophrenia (Arnold, 1992). NEUROSYPHILIS? Syphilis can be acquired either congenitally or, most often, by sexual contact with an infected individual. The primary stage is remarkably free of systemic signs, the patient is entirely well and usually free of fever but, at about 112 weeks after contact, 50% of females and 70% of males develop a primary lesion (chancre) at the site of infection by the spirochete Treponema pallidum. In the secondary stage, at 212 weeks after the primary stage, a skin rash appears. Constitutional symptoms that may accompany secondary syphilis include fever, weight loss, malaise, and anorexia. There follows an asymptomatic latent stage that may last decades. About 30% of untreated patients go on to develop tertiary lesions, but clinical disease occurs in only half of these cases; this fraction is 15% overall. About 80% of the tertiary lesions affect the cardiovascular system, 10% are chronic focal inflammations (gummas) in the liver and other sites, and up to 10% involve the central nervous system (neurosyphilis), i.e. 1.5% overall (Robbins, 1957). The major clinical categories of symptomatic neurosyphilis are meningovascular and parenchymatous syphilis. The latter includes tabes dorsalis, characterized by degeneration of the posterior columns of the spinal cord and posterior spinal roots. The interval from infection to expression of symptoms is about 27 years. Another form of parenchymatous syphilis, general paresis of the insane, is associated with direct invasion of T. pallidum into the brain. For unknown reasons the syndrome is more common in males. The average interval from infection to onset of general paresis is 20 years. The course of the untreated disease is inexorably progressive (Goodman & Karakuis, 1988). Neither the gamut of his symptoms nor the time course of his crises fits neurosyphilis. Vincent was treated for gonorrhea in The Hague in mid-1882 at age 29. He may have had a recurrence in Antwerp in 1885-86, at age 32. Even if he had contracted syphilis in The Hague, the major crises in Arles (age 35) would have been extraordinarily early for the onset of neurosyphilis, and his lengthy remissions from illness also negate the possibility. Mercury treatments were used at Arles and St. Re´my for syphilis, but Doiteau and Leroy (1928) found no indication that Vincent received mercury. LEAD POISONING About one-third of patients with excessive exposure to lead suffer colicky, abdominal pain. Fatigue, joint pains, headache, and irritability are also quite common. Impotence, constipation, vomiting, diarrhea have all been observed to some extent. Subtle effects on personality, memory, and learning ability are frequently associated with chronic lead poisoning. However, seizures and confusional states are less common, especially in adults (Dagg et al., 1965; Ellenhorn & Barceloux, 1988). Lead may be the oldest recognized chemical toxin; reports of occupational lead poisoning date to ancient Greece, and toxic levels have been found in Egyptian mummies. Artisans of leadglazed pottery and stained glass were particularly susceptible to intoxication until better conditions were adopted in the workplace. The ingestion of paints containing lead pigments has, even in recent times, presented a serious health hazard for children. Artists and craftsmen were exposed in the past because of their habit of wetting brushes orally and their accidental ingestion of lead-containing pigments from their tools and hands. Lead has an affinity for functional sulfhydryl groups in enzymes generally and a particularly sensitive example is d-aminolevulinic acid dehydratase. This is enzyme number two in the heme THE ILLNESS OF VINCENT VAN GOGH 37 biosynthetic pathway and its inhibition accounts for excessive excretion of d-aminolevulinic acid in the urine of lead-intoxicated patients. The last enzyme in the pathway, ferrochelatase, which catalyzes the incorporation of iron into protoporphyrin to form heme, is also inhibited by lead and this also contributes to the observed anemia (Ettenhorn & Barceloux, 1988). The excessive production of d-aminolevulinic acid in lead poisoning is similar to that found in acute intermittent porphyria, but note that porphobilinogen does not accumulate in lead poisoning. The similarity in neurological symptoms between AIP and lead poisoning may be referable to d-aminolevulinic acid. Abdominal pain, constipation, vomiting, paralysis, or paresis are very common in both AIP and lead poisoning. Neuropsychiatric symptoms are sometimes observed with lead intoxication, but much less frequently than in acute intermittent porphyria (Sassa, 1978). There was no chelation therapy for lead poisoning in Vincents time, and if his ingestion of lead salts (from his pigments) had been chronic, then the time course of such an illness would have been relentless and not episodic, as is well documented for van Gogh. ALCOHOLISM The extent of Vincents drinking is difficult to define, but we do know that he admitted to excesses. It is assumed that the hospital in Arles and the asylum at St. Re´my endeavored to restrict alcohol consumption; how successful they were is open to question; we do know that Theo paid a little extra at St. Re´my so that his brother could have wine with meals. I am convinced that Vincent engaged in social drinking when he visited friends in Arles, but this was for a relatively short time of a day or so. The time course of his illness, and the duration of some of the crises in the asylum, do not fit alcohol withdrawal syndrome per se.22 I believe it was more of a sensitivity to alcoholic beverages than an extraordinary dose. Alcohol is a an exacerbating factor for acute intermittent porphyria. Alcoholism and lead poisoning are reasonable suggestions but not standalone syndromes for van Gogh it is even less likely that the medical problems of Theo and sister Wil. would find much accommodation here. ME´NIE`RES DISEASE In 1861, Prosper Me´nie`re published several papers relating his observations on afflictions of the inner ear which caused nausea, vomiting, and vertigo. The disease was subsequently named after him and is characterized by hearing loss, vertigo, and tinnitus (ringing in the ears), and is usually unilateral (Harker & McCabe, 1980). During an attack of vertigo the patient is completely oriented to his surroundings and has no neurologic deficit such as paresthesia, diplopia, loss of consciousness, weakness, or paralysis. Sounds are distorted in the affected ear and are perceived as tinny. Loud sounds are intolerable or even painful, and hearing acuity gradually declines. Yasuda (1979) wondered in print, Was van Gogh suffering from Me´nie`res disease? The twelve page article was published in Japanese, but contains a full two pages of introduction and summary in English, more than enough to grasp the authors thrust. Those speculations received little support twenty years ago, because the diagnosis of Me´nie`res disease was based on a limited selection of symptoms. This dubious diagnosis was a sincere attempt, but it received little attention subsequently, except to be recorded in the most comprehensive bibliographies. The Journal of the American Medical Association, during the week of the centenary of Vincent van Goghs death, declared that, Van Gogh had Me´nie`res disease and not epilepsy (Arenberg et al., 1990). It was wrong on both counts; there is no case for Me´nie`res disease and epilepsy was no longer even the diagnosis of merit. A Colorado ear specialist and his colleagues had rediscovered Yasudas hypothesis and rewrote it as a definitive diagnosis. Their conclusion was based on a limited selection of symptoms, the pretense that 22Alcoholic seizures (rum fits) and delirium tremens occur after a heavy drinking bout. It is the signs that attend withdrawal that have some overlap with Vincents illness. 38 WILFRED NIELS ARNOLD epilepsy was the only viable alternative, and their propensity for construing certain complaints as hallmarks of the ear disease. Thus van Goghs gastrointestinal problems were taken to be strictly nausea and vomiting, several references to hearing voices were relegated to tinnitus, and the psychosis that was grave enough to cause selfmutilation and eventual suicide was underplayed. Their claim that van Gogh severed the lower half of his left ear to relieve tinnitus must surely strike readers, if not the editors of JAMA, as misplaced surgery.23 TOKENS There are many other working hypotheses by authors who are distinguished more by their conviction than common sense. Call-in talk shows on the radio are frequently their birthplace. Shortly after the publication of my book I encountered borderline personality disorder for van Gogh, which may be the exemplar for this type of offering. I thought that the title was enough to give the concept away but, to my astonishment, literature searches now turn it up in the form of published papers. The replacement child sentiment is another one in the same vein.24 I would continue to encourage organized skepticism as the first test. THE CHARM OF THE PAST There is an informal group that is keen to applaud the diagnostic skills of Vincents attending physicians. The old guys had it right after all is their banner. In their sea of indecision (sincere or deliberately compounded) this affords an island of safe haven blessed with nostalgia.25 Some have said that Dr. Rey (Arles) was brilliant and insightful. Their circular argument goes as follows: Rey embraced epilepsy without evidence of a full-fledged case; the commentators believe temporal lobe epilepsy (described many years later) is an attractive possibility; therefore they say Rey was ahead of his time. I join those who have judged Dr. Peyron as naive and trained in the wrong specialty, yet others have embraced as gospel his terse statements in the St. Re´my register. Tralbaut (1981) felt that the physicians of the south were overly influenced by the police reports in Arles, and by the patients own statements about a family history of epilepsy on his mothers side. If so, then the circle was indeed completed when Vincent wrote to Theo, as far as I can make out, the doctor here [Dr. Peyron] is inclined to consider what I have had [was] some sort of epileptic attack (letter 591). Theo van Gogh died in a mental institution in Den Dolder on January 25, 1891. Some of their medical records were released to Dutch newspapers in 1990, by a local archivist. The story, which covered the 38 days from Theos move out of Paris to Den Dolder until his death, ends dramatically, the final diagnosis was dementia paralytica [general paresis, a form of neurosyphilis]. At last the answer was out! Perhaps Vincent had the same thing?26 Dementia paralytica was described by Bayle, as early as 1822. Quincke is credited with introducing the lumbar puncture procedure together 23I have only one pleasant memory of this fiasco. While in Brisbane, Australia, as a guest for their van Gogh art exhibition in 1994, I was taken by a friend I have known since primary school to a beer garden. There he insisted on introducing me to everybody, eventually including a fellow in short pants and a singlet who was bouncing from table to table selling lottery tickets. Dr. Arnold is here for the big van Gogh affair, he is going to lecture tomorrow on van Goghs illness. We were both surprised by the smile of hidden wisdom and, I know mate, its Me´nie`res disease, my uncle had it. Alas, the misplaced power of immediate experience others have seen this in connection with manic depressive illness. 24The facts do not support the thesis (Arnold, 1995). However, it is even more bizarre to read that this sort of thing has been projected in some quarters as the crux of van Goghs underlying illness. 25In another setting the same group would supposedly be happy enough to acknowledge the laboratory developments that have advanced 20th century medicine. 26For reasons that still escape me the art politicians of Holland act as if the label of syphilis for the van Gogh brothers carries less social stigma than say alcoholism, let alone an inherited metabolic disease. Is this a misplaced attempt to protect the van Gogh family? THE ILLNESS OF VINCENT VAN GOGH 39 with examination of the cerebral spinal fluid for spirochetes, in 1892. Today, a definitive diagnosis would be based on serology of the cerebral spinal fluid, but this technology was not available until well into the twentieth century. General paresis was overly diagnosed in the nineteenth century. The psychiatric and neurological symptoms recorded from Theos case are far from definitive. An autopsy examination could have provided confirming evidence but apparently was not performed. In any event, the time course of Theos illness makes the case for neurosyphilis highly unlikely (Arnold, 1992). Dr. Paul Gachet also inherited his share of golden admiration. His ideas about Vincents illness are supposed to have included turpentine poisoning and the effects of too intense sun on a Nordic brain (Beer, 1935, p. 40). I have not been able to confirm the attribution to Dr. Gachet but I assume some verbal anecdote that slipped into the van Gogh literature. Vincent himself remarked upon being dazed with the sun (letter 512) that beats down on ones head . . . [and] makes one crazy (letter B15). Vincent may have been a bit reckless in his exposure but there was certainly more to his illness than heatstroke. The time course and the rest of the symptomatology cannot be accommodated under this heading.27 Rey, Peyron, and Gachet did their best to protect and rehabilitate the artist during those demanding two years. My observations within this section are not intended to disparage the van Gogh physicians but rather to make an appeal for placing their relative merits in perspective. They had the advantage of being there, but they were without benefit of the biochemical tools that we now take for granted. RESISTANCE FROM ART HISTORIANS, CURATORS, DEALERS, AND THE STATE MUSEUMS The art world harbors some people who deny any interest in van Goghs underlying illness. This position, albeit at odds with the public, takes various forms.Thus a catalog essaymay either skip over the subject or be content with he died by his own hand in 1890. During themonths of one blockbuster exhibition the museums education department managed to dodge a public lecture onVincentsmedical problems in favor of one recounting the provenance on the painting that fetched the best price at auction. Moreover, the vehemence with which so many art curators and dealers resist scientific enquiry suggests an unwholesome desire to maintain the mystique in order to protect the art.28 They do an injustice by assuming that the consumer of art needs protection. On the contrary, I believe that an explanation of Vincents underlying illness and the role of the environmentwill enhance rather than diminish genuine interest in van Goghs creations. The commercial interests of dealers and the ambitions of museums with regard to van Gogh foster the titillating connection between creativity and madness. Even if they are privately persuaded otherwise, they are reluctant to change something that they think is working. Newspaper and television journalists are reluctant to engage them on that turf and surely that is part of the reason for perpetuating the lengthy lists of possible van Gogh illnesses. They want to keep the subject vague in order to maintain the mythology. CONCLUDING REMARKS The house of Dr. Paul Gachet in Auvers-sur-Oise was recently opened to the public to coincide with 27I do not mean to defeat the message of this section but consider the following from an AIP expert, exposure to oil-based paints and solvents will, in some porphyrics, produce symptomatology including psychosis, colic, seizures, and neuropathy. Very rarely in acute porphyria, extreme exposure to sunlight may provoke an attack (Peters, 1986). Bonkovsky and I showed that pinene (turpentine) is porphyrogenic but sunlight! Was the good Doctor Gachet blessed? 28A curator at the Boston Museum of Fine arts once told me that he could not understand why anyone was interested in van Goghs illness. I ventured that at least it had something to do with his premature demise. No response, so I volunteered that Picasso and Matisse could have been contemporaries with Vincent if he had enjoyed a predicted lifespan of about 66 years how wonderful it would have been to have those three guys in the same room? Van Gogh painted lots of pictures anyway. 40 WILFRED NIELS ARNOLD the 150th anniversary of the birth of his most famous patient. Willem van Gogh, a greatgrandnephew of Vincent van Gogh, was in the crowd and he said he was touched to be present (New York Times, April 1, 2003). For those of us interested in round numbers it is also a propitious time to review the medical problems of the artist. A careful review of data from the artists letters and other contemporary sources indicates that Vincent suffered from an inherited disorder manifested by severe and manifold neurological problems, ranging from gastrointestinal pains to fits with hallucinations. His condition was exacerbated by his modus vivendi, which was marked by inadequate nutrition, abuse of alcoholic beverages, chronic smoking, environmental exposure, and the development of an abnormal affinity (pica) for terpenes. The intermittent nature of his illness, the sudden onset of crises, and the rapid return to normalcy after each episode, are all notable. The gamut of symptoms is best explained by a toxic psychosis. Within that category, the disease entity which most closely fits all of the data is acute intermittent porphyria [AIP], which was adopted by Loftus and Arnold (1991) and Arnold (1992) as a working hypothesis for Vincents underlying illness. This retrospective diagnosis has been compared and contrasted with other suggestions in the literature. The first case was described in a Dutch medical journal (Stokvis, 1889). AIP was not understood in Vincents time; even today it tends to be under-diagnosed. 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New York, Oxford University Press. Harker LA, McCabe BF (1980): Menieres disease and other peripheral labyrinthine disorders. In: Paparella MM, Shumrick DA, eds., Otolaryngology, 2nd edition, chapter 41. Philadelphia, WB Saunders. Hemphill RE (1961): The illness of Vincent van Gogh. Proc Roy Soc Med 54: 10831088. Hulsker J (1990): Vincent and Theo van Gogh: A Dual Biography. Ann Arbor, Fuller Publications. Jackson JH (1931): Selected Writings of John Hughlings Jackson. London, Hodder & Stoughton. Jamison KR (1993): Touched With Fire: Manic Depressive Illness and the Artistic Temperament. New York, Free Press: Maxwell Macmillan. Jaspers K (1922): Strindberg und van Gogh. Leipzig, Ernst Bircher. Johnson HA (1934): No madman. Art Digest 8: 11. Kappas A, Sassa S, Galbraith RA, Nordmann Y (1989): The porphyrias. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds., The Metabolic Basis of Inherited Disease. New York, McGraw-Hill, 6th edition, pp. 13051365. Knudsen KB, Sparberg M, Lecocq F (1967): Porphyria precipitated by fasting. New Engl J Med 277: 350-351. Kra¨epelin E (1921): Manic-depressive Insanity and Paranoia (Translated by RM Barclay). Edinburgh, Livingstone, 8th edition. Laiwah AACY, Mactier R, McColl KEL, Moore MR, Goldberg A (1983): Early-onset chronic renal failure as a complication of acute intermittent porphyria. Quart J Med 52: 9298. Lee TC (1981): Van Goghs vision: digitalis intoxication? JAMA 245: 727729. Lip GYH, McColl KEL, Goldberg A, Moore MR (1991): Smoking and recurrent attacks of acute intermittent porphyria. BMJ 302: 507. Loftus LS, Arnold WN (1991): Vincent van Goghs illness: acute intermittent porphyria. BMJ 303: 15891591. Lubin AJ (1972): Stranger on the Earth; A Psychological Biography of Vincent van Gogh. New York, Holt, Rinehart Winston. Monroe RR (1978): The episodic psychoses of Vincent van Gogh. J Nerv Ment Dis 166: 480488. Monroe RR (1992): Creative Brainstorms. New York, Irvington. Moore MR (1980): International review of drugs in acute porphyria. Int J Biochem 12: 10891097. Navratil L (1959): Vincent van Gogh: his disease assessed in the light of his paintings. CIBA Found Symp 7: 210216. Niedermeyer E (1983): Epilepsy Guide. Diagnosis and Treatment of Epileptic Seizure Disorders. Baltimore & Munich, Urban & Schwarzenberg. Penfield W, Jasper H (1954): Epilepsy and the Functional Anatomy of the Brain. Boston, Little, Brown and Co. Perry I (1947): Vincent van Goghs illness: a case record. Bull Hist Med 21: 146172. Peters HA (1986): Acute Hepatic Porphyria. In: Johnson RT, ed., Current Therapy in Neurologic Disease 1985-1986. New York, BC Decker, pp. 317321. Pickvance R (1984): Van Gogh in Arles. New York, Harry N. Abrams Inc. Pickvance R (1986): Van Gogh in Saint-Re´my and Auvers. New York, Harry N. Abrams Inc. Pinel P (1818): Nosographie Philosophique ou la Me´thode de lAnalyse Applique´e a la Me´dicine. Paris, Brosson, 6th edition. Prinzhorn H (1972): Artistry of the Mentally Ill (Translated by E von Brockdorff). New York, Heidelberg, Berlin, Springer-Verlag. (Original German version: Prinzhorn H. 1922. Bildnerei der Geisteskranken. Berlin: Verlag Julius Springer.) Rewald J (1986): Theo van Gogh as an art dealer. In: Gordon I, Weitzenhoffer F, eds., Studies in Postimpressionism. New York, Harry Abrams Inc, pp. 7115. Ridley A (1969): The neuropathy of acute intermittent porphyria. Quart J Med 38: 307333. Robbins SL (1957): Textbook of Pathology With Clinical Applications. Philadelphia & London, WB Saunders Co. Rothenberg A (1990): Creativity and Madness, New Findings and old Stereotypes. Baltimore and London, The Johns Hopkins University Press. Sarwer-FonerGJ (1988): The course ofmanic-depressive (bipolar) illness. In: Georgotas A, Cancro R, eds., Depression andMania.NewYork, Elsevier, chapter 4. 42 WILFRED NIELS ARNOLD Sassa S (1978): Toxic effects of lead, with particular reference to porphyrin and heme metabolism. In: De Matteis F, Aldridge WN, eds., Heme and Hemoproteins. Berlin, Springer-Verlag. Schmidt H (1915): lAbsinthe. lAlie´nation mentale et la criminalite´. Rapport fait au nom de la commission dhygie`ne publique de la chambre des de´pute´s. Annales dHygiene Publique et de Me´dicine Le´gale 23: 121133. Schnier J (1950): The blazing sun: a psychological approach to van Gogh. Am Imago 7: 143162. Sollmann T (1948): A Manual of Pharmacology and its Applications to Therapeutics and Toxicology. Philadelphia & London: WB Saunders Company, 7th edition. Stokvis BJ (1889): Over twee zeldzame kleurstoffen in urine van zieken. Weekblad van het Nederlandsch Tijdschrift voor Geneeskunde 2: 409417. Tralbaut ME (1981): Vincent van Gogh. New York, The Alpine Fine Arts Collection. van Gogh VW (1978): The Complete Letters of Vincent van Gogh Boston, New York Graphic Society, Vols. IIII, 2nd edition. van Gogh-Bonger (1978): Memoir of Vincent van Gogh. In: van Gogh VW, ed., The Complete Letters of Vincent van Gogh. Boston, New York Graphic Society, Vol. I, 2nd edition, pp XVLIII. Vinchon J (1960): Diagnostic de la folie de van Gogh. Historie de la Me´decine Communications pre´sente´es a` Paris a` la Socie´te´ Francaise dHistoire de la Me´decine en 1960, pp. 23-24. Voskuil PHA (1983): The epilepsy of Fyodor Mikhailovitch Dostoevsky (18211881). Epilepsia 24: 658667. Waldenstro¨m J (1937): Studien ueber Porphyrie. Acta Med Scand 82(Suppl.): 1254. Waldenstro¨m J (1957): The porphyrias as inborn errors of metabolism. Am J Med 22: 758773. Welland FH, Hellman ES, Gaddis EM, Collins A, Hunter GW Jr, Tschudy DP (1964): Factors affecting the excretion of porphyrin precursors by patients with acute intermittent porphyria. I. The effect of diet. Metabolism 13: 232250. Willis T (1672): De anima brutorum: Oxonii: R. Davis. Translated by S. Porage. In: Practice of Physick as Two Discourses Concerning the Soul of Brutes. London, Dring, Harper, Leigh (1683), Vol. I, p. 188. Withering W (1785): An Account of the Foxglove and Some of its Medical Uses: with Practical Remarks on Dropsy and other Diseases. Birmingham, GGJ & J Robinson. (This book was reproduced under the same general title, with annotations by Aronson JK (1985): London, Oxford University Press). Yasuda K (1979): Was van Gogh suffering from Me´nie`res disease? Otologia Fukuoka 25: 14271439.ier J (1950): The blazing sun: a psychological approach to van Gogh. Am Imago 7: 143162. Sollmann T (1948): A Manual of Pharmacology and its Applications to Therapeutics and Toxicology. Philadelphia & London: WB Saunders Company, 7th edition. Stokvis BJ (1889): Over twee zeldzame kleurstoffen in urine van zieken. Weekblad van het Nederlandsch Tijdschrift voor Geneeskunde 2: 409417. Tralbaut ME (1981): Vincent van Gogh. New York, The Alpine Fine Arts Collection. van Gogh VW (1978): The Complete Letters of Vincent van Gogh Boston, New York Graphic Society, Vols. IIII, 2nd edition. van Gogh-Bonger (1978): Memoir of Vincent van Gogh. In: van Gogh VW, ed., The Complete Letters of Vincent van Gogh. Boston, New York Graphic Society, Vol. I, 2nd edition, pp XVLIII. Vinchon J (1960): Diagnostic de la folie de van Gogh. Historie de la Me´decine Communications pre´sente´es a` Paris a` la Socie´te´ Francaise dHistoire de la Me´decine en 1960, pp. 23-24. Voskuil PHA (1983): The epilepsy of Fyodor Mikhailovitch Dostoevsky (18211881). Epilepsia 24: 658667. Waldenstro¨m J (1937): Studien ueber Porphyrie. Acta Med Scand 82(Suppl.): 1254. Waldenstro¨m J (1957): The porphyrias as inborn errors of metabolism. Am J Med 22: 758773. Welland FH, Hellman ES, Gaddis EM, Collins A, Hunter GW Jr, Tschudy DP (1964): Factors affecting the excretion of porphyrin precursors by patients with acute intermittent porphyria. I. The effect of diet. Metabolism 13: 232250. Willis T (1672): De anima brutorum: Oxonii: R. Davis. Translated by S. Porage. In: Practice of Physick as Two Discourses Concerning the Soul of Brutes. London, Dring, Harper, Leigh (1683), Vol. I, p. 188. Withering W (1785): An Account of the Foxglove and Some of its Medical Uses: with Practical Remarks on Dropsy and other Diseases. Birmingham, GGJ & J Robinson. (This book was reproduced under the same general title, with annotations by Aronson JK (1985): London, Oxford University Press). Yasuda K (1979): Was van Gogh suffering from Me´nie`res disease? Otologia Fukuoka 25: 14271439. "Remember.Research is the key to your cure!"
Diagnostic Testing for the Acute Porphyrias - ***** Clarification of Testing Results*****
Tuesday - May 19, 2015 @ 10:30:03
Diagnostic Testing for the Acute Porphyrias - Clarification of Testing Results
It has come to our attention that some patients who have been diagnosed clinically as having Acute Intermittent Porphyria (AIP) or another acute hepatic porphyria could not be confirmed by either biochemical or DNA testing. Biochemical testing is the demonstration of increased urinary ALA and PBG, and these values are highest during an acute attack when patients are symptomatic. Some patients can have high levels in between attacks as well, but not all. Positive diagnostic values should be increased greater than 5 times normal, not just a slight increase (less than 3 times normal) which can occur with dehydration. Most commercial laboratories and in particular the Porphyria Lab at the University of Texas Medical in Galveston which is run by Dr. Karl Anderson, will perform these tests properly. It is important that the doctor order urinary ALA and PBG and not a "porphyrin profile."
DNA, or molecular genetic testing, for the acute porphyrias is performed by sequencing the causative gene for the three major acute porphyrias and finding a specific pathogenic lesion on the gene, called a mutation. The technique used for DNA testing is at least 98% accurate, and patients with significantly elevated PBG are most often found to have a specific mutation. In our experience of testing over 1000 patients with or without elevated urinary PBG, only a few cases did not have a specific mutation. For these patients, we undertake special testing to look for gene deletions or other aberrations that would be responsible for a cryptic mutation.
During the last few years, our experience with DNA testing for the acute hepatic porphyrias has revealed certain mutations which are not pathogenic but are relatively frequent in normal individuals who do not have any acute hepatic porphyric symptoms. These are called polymorphisms and they are benign. When we recognize patients who have such polymorphisms, we continue to look further at their DNA to see if we can find a pathogenic mutation in addition. If no pathogenic mutation is found, we would have to classified or reclassify these patients as not affected. As you may be aware this has created great concern for patients who respond well to acute porphyria treatment that their treatment would be discontinued. We appreciate this concern and would like to have such patients physicians contact us so that we can discuss their situation, recommend additional testing to determine if their symptoms may have been misdiagnosed and institute appropriate treatment.
Diagnosing Acute Porphyria
The acute porphyrias include Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and d-Aminolevulinic Acid Dehydratase Porphyria (ADP). AIP is the most common of the acute porphyrias. The most common symptoms are acute attacks of severe abdominal pain, back pain, pain in the arms and legs, nausea, vomiting, rapid heartbeat and other symptoms. These attacks generally last for several days, and can be sporadic or happen frequently (~once/month). These acute attacks are very rare in children before puberty. These acute attacks are very rare in children before puberty. Attacks are often provoked by certain drugs, alcohol, hormones, infections, and perhaps stress. HCP and especially VP may cause blistering skin photosensitivity as well as acute attacks; AIP has no skin involvement, it is characterized just by these acute attacks.
A diagnosis of one of the acute porphyrias is made in two ways:
By biochemical testing:
For AIP- a urine porphobilinogen (PBG) test during an acute attackthe urine PBG level will be very high if the symptoms are caused by an acute porphyria (greater than 5 times the normal value)
For HCP and VP- a urine porphobilinogen (PBG) test during an acute attack if the patient has acute symptoms, or plasma porphyrins if the patient has skin symptoms
By genetic testing looking at the genes known to cause the acute porphyrias
There are many misconceptions about the urine PBG testing, its reliability, and urine color of patients with acute porphyria. The urine sample for PBG testing needs to be protected from light; the sample should be wrapped in tin foil or placed in a brown opaque bag after collection. However, if the sample is exposed to light for a little while (a few minutes) this will not affect the results. Please follow the directions provided by the laboratory when doing this testing.
Urine PBG testing can be sent to many labs including Quest, LabCorp, Mayo, ARUP, UTMB and Mount Sinai; they all do this testing reliably.
Many patients have urine that is red/purple in color when they have an acute attack, but this is not always the case. Patients can still have elevated urine PBG levels even if their urine color is normal. These misconceptions may lead to improper testing, or misdiagnoses. Physicians who suspect a patient has an acute porphyria should call one of the expert Porphyria centers in the US to consult (http://www.rarediseasesnetwork.org/porphyrias/index.htm).
The Difference between Active and Latent Acute Porphyria
It is important to know that ~80% of people who have changes in their porphyria genes (called mutations) never have symptoms of the acute porphyrias. These people are said to have latent acute porphyria.
If someone has a mutation in an acute porphyria gene and reports symptoms similar to an acute attack, their urine PBG level should be checked. If the urine PBG level is normal then there is likely another cause to this persons symptoms. Acute attacks are distinguished from other conditions that cause abdominal pain by very high PBG levels.
Treatment of Acute Porphyria
For patients with confirmed diagnoses, during acute attacks Panhematin infusions are administered as treatment and the pain is managed with various other medications. For more information on Panhematin please visit: http://www.aiporphyria.com/healthcare-professionals/treating-AIP/dosing
If someone who does not have a confirmed diagnosis of acute porphyria, documented by very high PBG levels, is having symptoms that seem consistent with an acute porphyria attack Panhematin is administered at the discretion of the treating physician. Generally all other causes of abdominal pain which are much more common than acute porphyria are ruled-out first. If Panhematin is administered and subsequently the diagnosis of acute porphyria cannot be confirmed by elevated urine PBG values or DNA testing, then it would be concluded that the attack is not caused by an acute porphyria. Even after Panhematin treatment, or after an acute attack has passed, the urine PBG levels should still be elevated for several days to a week. These levels may not be as high as they were during the acute attack, but will still be elevated.
Updated Brochures to Order from the APF for all Types
Friday - May 15, 2015 @ 10:30:03
Do you need materials from the APF. We offer several brochures for you and your Doctors. If you would like to purchase any of these and have them mailed to you directly please feel free to contact the APF @ 1-866-APF-3635. They are proving to be so helpful to many patients with all types of Porphyria so take a step up to educate yourself, your loved ones and your Doctors. Order yours today.
Pamphlets
US residents: The following brochures are $1.30 each.
International residents: The following brochures are $2.50 each.
Overview of Porphyria
Panhematin
Management of the Acute Porphyrias
Diet and Nutrition
Erythropoietic Protoporphyria
Porphyria Cutanea Tarda
If you would like to order any of these Pamphlets please call the APF Toll free: 1.866.APF.3635
"Remember.Research is the key to your cure!"
Carlos Johnson and his story of AIP. How he endures it! A must Read
Check out Victor Mejias Bent Rods Bass Club get involved for a great cause!
Friday - May 8, 2015 @ 10:30:01
BENT MINI RODS CHALLENGE
Bent Rods Bass Club is proud to host the: Bent mini Rods Challenge as our Charity Tournament for 2015 with all proceeds going to the American Porphyria Foundation.
Location: Deep Lake, Lake Villa, IL. Jack & Lydias Resort.
When: Sunday, July 26th Sunrise to Noon
Entry Fees: $20 per angler (all entry fees go to APF)
Each angler must turn in at least one kiddie pole at the end of the tournament that we will be donating to help get kids fishing.
Deep Lake is private and you must rent a boat from Jack & Lydias Resort. The cost is $15 a day, you can bring a trolling motor or outboard(10hp max) to use on their boats.
We will have a sign-up page soon.
Bent mini Rods Challenge Rules:
Rod & Reel You can have as many as you want but they must meet the requirements below: 3 foot or less in length You can lube reel & change line, no other modifications allowed Must be a character pole (ie: Barbie, Spiderman, Disney, etc)
Must have a current Illinois Fishing License
Bump Board, all fish must be photographed on bump board with token
Digital Camera, need camera or phone to take photos
All bass must be released immediately after photos
No live bait and no trolling
Must turn in one kiddie pole at end of Challenge
Sponsors needed! Since all entry fees are donated to Charity we need sponsors to donate the prizes, if you would like to help us with this event please email buster@bentrods.org
Victor A Mejias
"Remember.Research is the key to your cure!"
Learn more about EPP Facts!
Monday - May 4, 2015 @ 10:30:02
Erythropoietic Protoporphyria (EPP) or Protoporphyria
Erythropoietic Protoporphyria (EPP) or Protoporphyria
Erythropoietic Protoporphyria is characterized by abnormally elevated levels of protoporphyrin IX in erythrocytes (red blood cells) and plasma (the fluid portion of circulating blood), and by sensitivity to visible light that is usually noticed in early childhood and occurs throughout life. EPP can result either from mutations of the ferrochelatase gene (FECH), or less commonly the delta-aminolevulinic acid synthase-2 gene (ALAS2). When EPP is due to an ALAS2 mutation it is termed X-linked protoporphyria (XLP), because that gene is found on the X chromosome.
Protoporphyrin accumulates first in the bone marrow in EPP, and then in red blood cells, plasma and sometimes the liver. Protoporphyrin is excreted by the liver into the bile, after which it enters the intestine and is excreted in the feces. It is not soluble in water, so is not excreted in the urine.
EPP is the third most common type of porphyria, and the most common in childhood. It causes very painful photosensitivity and can greatly impair quality of life. Delay in diagnosis is greater than with any other type of porphyria.
Swelling, burning, itching, and redness of the skin may appear during or after exposure to sunlight, including sunlight that passes through window glass. This can cause mild to severe burning pain on sun-exposed areas of the skin. Usually, these symptoms subside in 12 to 24 hours and heal without significant scarring. Blistering and scarring are characteristic of other types of cutaneous porphyria but are unusual in EPP. Skin manifestations generally begin early childhood and are more severe in the summer.
There is an increased risk of gallstones, which contain protoporphyrin. Excess protoporphyrin can also cause liver damage. Less than 5% of EPP patients severe liver damage and a condition caused protoporphyric hepatopathy that sometimes requires liver transplantation.
Diagnosis and Genetic Counseling
EPP should be suspected in anyone with non-blistering photosensitivity especially when is it prolonged and beginning in childhood. It is easy to make a diagnosis, or rule it out, once it is suspected.
The diagnosis of EPP is established by finding an abnormally high level of total erythrocyte protoporphyrin, and showing that this increase is mostly free protoporphyrin rather than zinc protoporphyrin. There is considerable confusion about which test to order. Sometimes laboratories have measured only zinc protoporphyrin and reported results incorrectly as protoporphyrin or free erythrocyte protoporphyrin (FEP). Laboratories that measure total erythrocyte protoporphyrin, free protoporphyrin and zinc protoporphyrin and report results reliably are:
Porphyria Laboratory and Center, University of Texas Medical Branch at Galveston, 1-409-772-4661
Mayo Medical Laboratories, 1-800-533-1710
ARUP Laboratories
Porphyrins are almost always elevated in plasma in EPP, but may be normal in mild cases. Fecal porphyrins may be normal or increased.
An experienced biochemical laboratory can usually distinguish between patients with EPP and XLP, because the former have much less zinc protoporphyrin in their erythrocytes. This can be explained because in the marrow the enzyme ferrochelatase not only normally makes heme (iron protoporphyrin) from protoporphyrin and iron, but can also make zinc protoporphyrin, especially when excess protoporphyrin is present or iron is deficient. However, this does not replace DNA studies.
Rarely, EPP develops in adults in the presence of a bone marrow disorder such as polycythemia vera, and is due to expansion of a clone of red blood cell precursors in the marrow that is deficient in ferrochelase.
DNA studies are important for confirming the diagnosis of EPP and XLP and for genetic counseling. This should be completed first in a person known to have the disease, and the information about the mutations in that individual used to guide testing of family members.
When EPP is due to a FECH mutation the inheritance is described as autosomal recessive. It is most common to find that one severe mutation is inherited from one parent and another weak mutation inherited from the other parent. The weak mutation is quite common in normal Caucasians, rare in Blacks and even more common in Japanese and Chinese populations. This mutation is sometime referred to as hypomorphic because it results in formation of a less than normal amount of ferrochelatase. But is does not cause EPP unless it is paired with a severe mutation. The severe mutation is characteristic for an EPP family and is present in all affected individuals. Carriers of the severe mutation are not affected because they do not have the weak mutation. Affected individuals and unaffected carriers can transmit the severe mutation to the next generation. Some of their children will have EPP if the other parent has a copy of the weak mutation. Rarely, the weak mutation is absent in an EPP family and two severe mutations are found, with at least one producing some ferrochelatase.
In XLP, mutations of the ALAS2 gene, which is found on the X chromosome, causes an increase in the production of the enzyme ALAS2 in the bone marrow. Several of these gain of function mutations have been described in different XLP families. In XLP protoporphyrin production exceeds that needed for heme and hemoglobin formation. Like hemophilia and other X linked genetic diseases, XLP is more common in men. Women have two X chromosomes and are usually not affected because they have a normal as well as a mutated ALAS2 gene. Men have only one X chromosome and will be affected if they inherit an ALAS2 mutation. Women with an ALAS2mutation will, on average, pass that mutation to half of their daughters (who will usually be unaffected carriers) and to half of their sons (who will be affected).
Treatment and Management
1. Sunlight protection
Protection from sunlight is the mainstay of management of EPP, and this is necessary throughout life. Disease severity and porphyrin levels in erythrocytes and plasma probably remain high and relatively constant throughout life in EPP. However, this has been little studied and more longitudinal observations are needed. Life style, employment, travel and recreation require adjustment in order to avoid painful reactions to sunlight and even from exposure to fluorescent lighting. For these reasons EPP can substantially affect quality of life.
Protective clothing, including broad-brimmed hats, long sleeves, gloves and trousers (rather than shorts), is beneficial. Several manufacturers specialize on clothing made of closely woven fabrics for people with photosensitivity.
2. Beta-Carotene (Lumitene Tishcon)
Beta-carotene is an over the counter product that was originally developed in a purified form as a drug for the treatment of EPP, and was shown to be effective by Dr. Micheline Mathews-Roth at Harvard University and others. The pharmaceutical grade formulation is now distributed by Tishcon as Lumitene, and can be ordered by calling 1-800-866-0978 or via the website www.epic4health.com. Other products are less standardized and reliable and are not recommended.
Beta-carotene provides protection by quenching reactive oxygen products that form when protoporphyrin is activated in the skin by light. It is important to take an amount that is adequate to be protective. For more information about Lumitene, including a recommended dosing schedule, please see the Lumitene section of this website.
3. Other considerations
In an occasional patient, protoporphyrin causes liver problems, so monitoring liver function is important. EPP patients should also not use any drug or anesthetic which causes cholestasis (slowing down bile flow), and should also avoid alcohol. Women should avoid medications containing estrogen (birth-control pills, hormone replacement therapy), and men should avoid testosterone supplements, as these substances can also have deleterious effects on the liver of a person with EPP.
Consult a specialist. Because EPP is a rare condition, most physicians are not knowledgeable about it. Contact The American Porphyria Foundation, 713-266-9617 for contact with an expert and to provide further information. A Medic Alert bracelet with instructions to contact a specialist if needed is a worthwhile precaution.
Yearly monitoring. Testing to include erythrocyte total protoporphyrin, plasma porphyrin, complete blood counts, ferritin and liver function tests should be done yearly. Porphyry levels are expected to be stable and liver tests to remain normal. EPP patients may have evidence of iron deficiency, and an iron supplement may be advisable if the serum ferritin is below about 20 ng/mL.
Vitamin D. Because they avoid sunlight, EPP patients are likely to be deficient in vitamin D. A vitamin D supplement with calcium is recommended for bone health.
Liver protection. It is important to avoid other causes of liver disease that might promote the development of liver complications from EPP. Patients should avoid alcohol and other substances that might damage the liver, including many herbal preparations, and be vaccinated for hepatitis A and B.
Surgical lights. Strong operating room lights can cause photosensitivity of the skin and even surfaces of internal organs. Flexible membrane filters, such as CL5-200-X from Madico Co., are available to cover surgical lights and offer some protection. This is especially important in EPP patients with liver failure, which causes even greater increases in protoporphyrin levels and photosensitivity.
Drugs. Drugs that are harmful in other porphyrias are not known to make EPP worse, but are best avoided as a precaution. This may include estrogens and other drugs that might reduce bile formation. A short course of a non-steroidal anti-inflammatory drug can provide some pain relief after an episode of photosensitivity, but can cause ulcerations of the digestive track especially with prolonged use.
Laser treatment. According to Dr. Roth, laser treatments for hair removal or eye surgery have not been a problem in EPP people. But the doctor should be made aware of the diagnosis, and that laser output between 400 and 650 nanometers might be harmful. Before hair removal treatment, the doctor may irradiate a small area of the skin to be treated for the length of time it will take to do the hair removal to ascertain if the patient would react within the period of time that a reaction to sunlight would be expected in that patient.
Children with EPP. Avoiding sunlight can be difficult for children with EPP who have less sunlight tolerance than their friends. Camp Discovery is an option for such children. It provides a week-long summer camping experience of fishing, boating, swimming, water skiing, arts and crafts, and just plain fun for young people with skin disorders, and is sponsored by the American Academy of Dermatology. Full scholarships, including transportation, are provided by the American Academy of Dermatology through generous donations of their members and other organizations. Members of the Academy are asked to recommend candidates for Camp Discovery, so ask your child's doctor about sending your child to Camp Discovery.
Disneyland and Disney World are responsive to people with sun sensitivity. They will provide a pass to enable you to enter attractions without waiting in line in the sun.
Disneyland Go to "Town Hall" and explain your problem with photosensitivity. You should bring a physician's letter with you as well as an APF brochure explaining the type of Porphyria you have. The staff will ask you some questions about your limitations (e.g., whether or not you can climb stairs) and how many are in your group. Next time you return, be sure to bring the old card with you, as it will only take about half as long to go through the process on your next trip.
Disney World Proceed to the "Guest Relations" office at any park (Magic Kingdom, EPCOT, etc.) and request the Special Assistance Pass.
Remember to bring a doctor's note and explanation of your condition, because it is not necessarily visible. People on duty may not be familiar with light sensitivity and its consequences.
Research Opportunities
Patients with EPP and XLP can participate in the research through the Porphyrias Consortium. The American Porphyria Foundation has information on what research protocols are currently open.
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The Porphyrias Consortium is conducting a Longitudinal Study to better define the natural history of the disease. This study is currently open for enrollment of new patients.
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The Porphyrias Consortium will be starting a pilot study soon on a drug that may lower porphyrin levels in EPP.
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Clinuvel Pharmaceuticals is developing afamelanotide (Scenesse) for the treatment of EPP. This drug is given by injection and increases skin pigmentation. Another study of this drug is expected to open within the next year.
All patients with porphyria are encouraged to enter the Porphyrias Registry at the Porphyrias Consortium website. A link to this website is found on the website of the American Porphyria Foundation. Registration demonstrates to NIH that patients and their families think that research on porphyrias is important. You can also ask that one of the 6 porphyria center in the Consortium contact you.
"Remember.Research is the key to your cure!"
Directions For Collecting A 24-Hour Urine Sample for Acute Types of Porphyria
Friday - May 1, 2015 @ 10:30:01
Directions For Collecting A 24-Hour Urine Sample
Many members have asked about the proper way to collect a 24-hour urine. Here are the directions from one Porphyria laboratory. You might want to compare these directions with those from your own laboratory.
Please use a dark plastic jug for collecting the urine. The urine should be protected from light during collection and during shipping. Add 5 grams of sodium carbonate, a powder that will readily dissolve in the urine, to the jug. This adjusts the acidity of the urine and helps preserve the substances the lab will be measuring. It is not toxic or irritating.
A 24-hour urine collection must be started at a specific time and then ended at the same time the next day. You can choose any time that is convenient for you to start the collection. But you must also be sure that you can end the urine collection at the same time the next day.
Record the time that you have chosen to start the collection. You need to start the urine collection with an empty bladder. Therefore, at exactly this time, empty your bladder and discard the urine. In other words, when you start the urine collection, you should empty your bladder and not add that urine to the jug.
From that time on, add any urine that you pass to the jug. You do not need to record the time each time you urinate.
During the collection, store the urine jug tightly capped in a refrigerator or place it in an ice chest.
Exactly 24 hours after you start the urine collection, you should end the urine collection by emptying your bladder into the jug for the last time.
The American Porphyria Foundation promotes comprehensive care necessary for treating individuals with Porphyria. This section of our website offers suggestions for finding a local doctor who can manage your Porphyria, options for having your doctor consult a Porphyria specialist, and information on arranging a visit to a Porphyria clinic.
Because Porphyria is so rare, few physicians have experience treating patients with the disease. Most patients are in fact treated But the APF can help by putting your doctor's office in touch with a Porphyria specialist who can offer guidance on your care.
For those who need a diagnosis, you may be able to obtain a consultation at Porphyria clinic. Call the APF to reach a porphyria expert at a porphyria center. The APF office will also guide you to doctors who are not experts but are knowledgeable about porphyria. You may be asked to send your blood, urine, and stool samples for evaluation in advance of a clinic appointment. Especially if you plan to travel for a consultation, it is a good idea to call ahead and explain that you would like to be evaluated for Porphyria so that you can be sure you have done any necessary testing in advance. If local video conferencing facilities are available, telemedicine consultation with a Porphyria expert is also available.
Regardless of your situation, it is best to establish a good relationship with a doctor in your area. Developing a relationship with a primary care physician takes time and can be frustrating, particularly when you have difficulty finding a doctor who will manage your care. In this section of the website, you will also find Tips for the Doctor's Office that may help.
If you're having trouble finding a local doctor, the following organizations' doctor finder or physician referral services could be helpful. The APF does not recommend or endorse the doctors listed through these sites.
If you would like to read about supporting programs to ensure the quality of specialists in the field of porphyria, please see our Protect Our Future campaign information.
"Remember.Research is the key to your cure!"
Katie Fabian & EPP
Monday - April 27, 2015 @ 10:30:00
My name is Katie Fabian and I have EPP.
I was diagnosed very very young, after my mom discovered some behavior when I was exposed to the sun. I have had my share of ups and downs growing up. I have missed so many pool parties because they would be during the day. I had to cover up from head to toe when I played soccer and softball, and occasionally I would get a taste of the sun, making me very sick. During gym classes in school, I would have to cover up, and eventually I had to give up doing outdoor activities, and do physical activity articles instead, to keep my grade up. During the summer, I would wear shorts, t shirts, just to try to be "normal", but I suffered the consequences every time. I've learned now to do all of my activities in the evenings, to prevent me from having future attacks. When I get a reaction, I itch profusely, and my anxiety starts kicking in. My skin gets very pink, and sometimes purple, depending on the severity of the attack. The next day, my skin gets so swollen and I just feel so lethargic and sick to my stomach. I have many many blisters on my hands from the sun. "Remember.Research is the key to your cure!"
Diagnostic Testing for the Acute Porphyrias - Clarification of Testing Results
Thursday - April 23, 2015 @ 10:30:04
Diagnostic Testing for the Acute Porphyrias - Clarification of Testing Results
It has come to our attention that some patients who have been diagnosed clinically as having Acute Intermittent Porphyria (AIP) or another acute hepatic porphyria could not be confirmed by either biochemical or DNA testing. Biochemical testing is the demonstration of increased urinary ALA and PBG, and these values are highest during an acute attack when patients are symptomatic. Some patients can have high levels in between attacks as well, but not all. Positive diagnostic values should be increased greater than 5 times normal, not just a slight increase (less than 3 times normal) which can occur with dehydration. Most commercial laboratories and in particular the Porphyria Lab at the University of Texas Medical in Galveston which is run by Dr. Karl Anderson, will perform these tests properly. It is important that the doctor order urinary ALA and PBG and not a "porphyrin profile."
DNA, or molecular genetic testing, for the acute porphyrias is performed by sequencing the causative gene for the three major acute porphyrias and finding a specific pathogenic lesion on the gene, called a mutation. The technique used for DNA testing is at least 98% accurate, and patients with significantly elevated PBG are most often found to have a specific mutation. In our experience of testing over 1000 patients with or without elevated urinary PBG, only a few cases did not have a specific mutation. For these patients, we undertake special testing to look for gene deletions or other aberrations that would be responsible for a cryptic mutation.
During the last few years, our experience with DNA testing for the acute hepatic porphyrias has revealed certain mutations which are not pathogenic but are relatively frequent in normal individuals who do not have any acute hepatic porphyric symptoms. These are called polymorphisms and they are benign. When we recognize patients who have such polymorphisms, we continue to look further at their DNA to see if we can find a pathogenic mutation in addition. If no pathogenic mutation is found, we would have to classified or reclassify these patients as not affected. As you may be aware this has created great concern for patients who respond well to acute porphyria treatment that their treatment would be discontinued. We appreciate this concern and would like to have such patients physicians contact us so that we can discuss their situation, recommend additional testing to determine if their symptoms may have been misdiagnosed and institute appropriate treatment.
Diagnosing Acute Porphyria
The acute porphyrias include Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and d-Aminolevulinic Acid Dehydratase Porphyria (ADP). AIP is the most common of the acute porphyrias. The most common symptoms are acute attacks of severe abdominal pain, back pain, pain in the arms and legs, nausea, vomiting, rapid heartbeat and other symptoms. These attacks generally last for several days, and can be sporadic or happen frequently (~once/month). These acute attacks are very rare in children before puberty. These acute attacks are very rare in children before puberty. Attacks are often provoked by certain drugs, alcohol, hormones, infections, and perhaps stress. HCP and especially VP may cause blistering skin photosensitivity as well as acute attacks; AIP has no skin involvement, it is characterized just by these acute attacks.
A diagnosis of one of the acute porphyrias is made in two ways:
By biochemical testing:
For AIP- a urine porphobilinogen (PBG) test during an acute attackthe urine PBG level will be very high if the symptoms are caused by an acute porphyria (greater than 5 times the normal value)
For HCP and VP- a urine porphobilinogen (PBG) test during an acute attack if the patient has acute symptoms, or plasma porphyrins if the patient has skin symptoms
By genetic testing looking at the genes known to cause the acute porphyrias
There are many misconceptions about the urine PBG testing, its reliability, and urine color of patients with acute porphyria. The urine sample for PBG testing needs to be protected from light; the sample should be wrapped in tin foil or placed in a brown opaque bag after collection. However, if the sample is exposed to light for a little while (a few minutes) this will not affect the results. Please follow the directions provided by the laboratory when doing this testing.
Urine PBG testing can be sent to many labs including Quest, LabCorp, Mayo, ARUP, UTMB and Mount Sinai; they all do this testing reliably.
Many patients have urine that is red/purple in color when they have an acute attack, but this is not always the case. Patients can still have elevated urine PBG levels even if their urine color is normal. These misconceptions may lead to improper testing, or misdiagnoses. Physicians who suspect a patient has an acute porphyria should call one of the expert Porphyria centers in the US to consult (http://www.rarediseasesnetwork.org/porphyrias/index.htm).
The Difference between Active and Latent Acute Porphyria
It is important to know that ~80% of people who have changes in their porphyria genes (called mutations) never have symptoms of the acute porphyrias. These people are said to have latent acute porphyria.
If someone has a mutation in an acute porphyria gene and reports symptoms similar to an acute attack, their urine PBG level should be checked. If the urine PBG level is normal then there is likely another cause to this persons symptoms. Acute attacks are distinguished from other conditions that cause abdominal pain by very high PBG levels.
Treatment of Acute Porphyria
For patients with confirmed diagnoses, during acute attacks Panhematin infusions are administered as treatment and the pain is managed with various other medications. For more information on Panhematin please visit: http://www.aiporphyria.com/healthcare-professionals/treating-AIP/dosing
If someone who does not have a confirmed diagnosis of acute porphyria, documented by very high PBG levels, is having symptoms that seem consistent with an acute porphyria attack Panhematin is administered at the discretion of the treating physician. Generally all other causes of abdominal pain which are much more common than acute porphyria are ruled-out first. If Panhematin is administered and subsequently the diagnosis of acute porphyria cannot be confirmed by elevated urine PBG values or DNA testing, then it would be concluded that the attack is not caused by an acute porphyria. Even after Panhematin treatment, or after an acute attack has passed, the urine PBG levels should still be elevated for several days to a week. These levels may not be as high as they were during the acute attack, but will still be elevated.
Some historians have speculated that King George III of England suffered from Variegate Porphyria. According to notes made by the physicians attending him at that time, he suffered symptoms similar to those seen in an acute attack of porphyria: abdominal pain, constipation, rashes, confusion and severe weakness in his limbs. They also mentioned that he had dark reddish urine during these sieges and that he was often "mad." The royal physicians were not permitted to conduct extensive physical examinations, so they had to depend on what King George told them about his condition.
On one occasion when he was having a relapse of his mental and physical symptoms, Parliament debated his ability to maintain his position as King. Interestingly, he spontaneously recovered. Since George III ruled during the American Revolution, he was thought to have had a significant impact on Britains loss to the revolutionaries. His mental and physical lapses were blamed for much of the mishandling of the war. In 1811, George suffered a severe relapse and subsequently was dethroned by the Prince of Wales.
After researching the physicians' reports, Drs. Ida Macalpine and Richard Hunter proposed that King George might have had one of the acute porphyrias. They published their theory in the British Medical Journal in 1966 and later wrote a book, George III and the Mad Business, which presented more detailed accounts of King George's malady. It is important to note that a number of Porphyria specialists and other physicians disagree with their theory. However, over the years it has been widely publicized.
** King George Letter **
You Can Own a Piece of History
An APF member purchased a handwritten letter by King George III from a reputable dealer in rare documents. He did this so that other APF members might have a superb replica of the letter as a keepsake.
King George might be your relative since it is now known through scientific studies that King George had porphyria, too. He sat on the English throne for sixty years.
Interestingly, some historians firmly believe that his illness so impacted the English rule of the Colonies that the powerful British troops lost the Revolutionary War.
Included in this package are:
A replica of the letter written in George's own hand which is reprinted on high quality paper similar to the original. A transcription of the letter A brief history of King George III and the impact of his porphyria illness on his own life and British rule. These items are suitable for framing and are enclosed in an attractive folder.
You Can Own a Piece of History â?¢ $50.00 for US residents â?¢ $60.00 for International residents An APF member purchased a handwritten letter by King George III from a reputable dealer in rare
PORPHYRIAFOUNDATION.COM
Amy Chapman AIP Story Supports #NPAW
Monday - April 20, 2015 @ 10:30:02
Amy Chapman
Type of Porphyria:
Acute Intermittent Porphyria (AIP)
My name is Amy Chapman, and I am 40 years old.
I was diagnosed with AIP on December 19, 2007, by Dr. Karl Anderson at the University of Texas Medical Branch (UTMB) Porphryia Center in Galveston. I am the first one in my family to receive Panhematin, and also the first to have my DNA tested at the Mount Sinai Porphyria Clinic so that other family members could be tested for the disease even if they are not ill. I am also involved in an AIP study with Mount Sinai now.
It took me a total of five times to get the tests done right. All along I was constantly sick. Since I was diagnosed, my attacks have been treated with Panhematin infusions over six different hospitals stays, ranging from 4 to 14 days.
Looking back, for years before my diagnosis, I was sick every three weeks on average. In addition to porphyria, I have always been prone to colds and sinus infections, and every time I have one, like clockwork, an AIP attack follows. I would go to the doctor and receive medicine, but nothing worked. I had severe stomach pain, muscle pain, and nerve pain; I had nausea and headaches; I couldnt remember things and was nervous; my blood pressure was high; and I had severe constipation for days into a week. At one point they gave me medication for high blood pressure, but it didnt work.
It was terrible for my husband, my family, and me! One time, even after my diagnosis I went in to a local emergency room with my personalized ER Kit from the American Porphyria Foundation, including my diagnostic test results, contact information for the Foundation and instructions on what to do to make me feel better. I asked them to call the APF and to speak with Dr. Anderson at UTMB. But the doctors were not familiar with my diagnosis. Finally, a resident who had studied AIP a bit admitted me to the hospital.
I took it upon myself to learn from my mother and on my own so that I could educate my doctors and help them understand my disease. All these years I was taking all the wrong medications and it was making my health worse. So when I got diagnosed, I changed to all safe medications on Dr. Andersons instructions.
One day, my mother found a hospital in Grand Rapids, MI that was familiar with AIP. They had just learned about the disease and Panhematin therapy. When I went in that day, I could not function. My blood pressure very high, and I had pain so severe I could hardly speak or move. I was not eating and had pain in my muscles and a headache. I was nervous, had high sugar and constipation, but the staff worked so quickly and kept a close eye on me.
The Panhematin came off the plane the next morning, and Dr. Anderson spoke with the physician treating me and advised him on how to care for me. I was able to show my doctor the APF website, and he went home and read through all the information related to treating AIP. He asked me questions daily and listened and believed me. And each day I went through my own checklist to make sure of the timing of my medications. I will always speak up to remind them if something is not in place and the nurses quickly correct the issue. I walked out of the hospital feeling so much better, and smiling. I was a new person. Panhematin works so well for me!
The hospital staff held a meeting to educate the nurses and pharmacists, and they came in to speak with me on a daily basis. I learned so much. My last attack was in December 2009, and I first went to the hospital when, along with all of my usual symptoms, I developed a new one: I was paralyzed from the waist down. My husband picked me up and reassured me that I would be OK, and in six days I walked out of the infusion center feeling so much better.
I am always learning, researching and asking questions, and I truly appreciate Lundbeck, Inc. (maker of Panhematin), the Porphryia Foundation, and the doctors, nurses and pharmacists who have helped me. I also appreciate the support and patience of my family. Each person in a patients life plays an important part in helping them. We need to spread the word about this rare disease, and make it known in the medical field, so that all can be treated quickly and properly. In the end, effective treatment may mean saving the patients life.
I was only seventeen years old when I suffered my first attack of porphyria. The onslaught of pain was rapid and vicious. When I was asked by the attending physician to describe the pain, I likened the agony to that caused by a thousand flaming swords imbedded deeply in my abdomen. Unfortunately, my physicians, who were unable to find any explanation for my condition, viewed my seemingly exaggerated description with an air of disbelief. Their wariness was further validated when the undiagnosed pain and accompanying weakness disappeared after a few days without any apparent treatment. What a fluke; we thought. The obvious medical explanation for the short-lived episode was simply that I was an over-anxious, young woman with little tolerance for menstrual cramps and a notion for hypocondriasis. Although I knew that this was not the case, I thought no more of the horrendous bout with pain and promptly returned to my studies and active life as a high school senior.
Several years later, the long forgotten pain reappeared with a vengeance. I was hospitalized and tested repeatedly to no avail. Nothing conclusive was ever indicated on the tests, so the same sad "hypochondriac" conclusion was drawn. Since I prided myself on my sense of independence and responsibility, I was taken aback by such insinuations.
From that point on, I was wary of disclosing to anyone the intensity of my pain and the severity of the other encroaching symptoms lest I subject myself again to undue embarrassment. By then I was living with a myriad of rather generic but caustic symptoms all of which waxed and waned with cyclical frequency: severe abdominal pain, extreme weakness, tachycardia, labored breathing, crushing chest pain, a mercurial disposition and a battery of frightening tiny seizures and strange, purplish urine. Over a period of time, I could no longer conceal the worsening symptoms and concluded once again that I needed to find a name for the illness that was quickly bringing my life to a close.
Fortunately, at a social gathering, Dr. George Penton, a physician friend in Montgomery, Alabama, noted the painful grimace on my face and my strange metallic grey pallor and asked if I was feeling ill. I quickly explained my present symptoms as well as the prior series of misdiagnoses which had caused my subsequent hesitation to seek any additional medical care. Dr. Penton suggested that I might consider enduring a few more tests and assured me that he would press on to an answer.
Dr. Penton repeated the myriad of examinations I had taken previously and again found all the results to be normal. Nonetheless, he did as he promised and continued to pursue a definitive diagnosis by scheduling another protracted series of diagnostic tests. The only test in the next series that proved abnormal was the encephalogram, which indicated only minor petit mal seizure activity. The report gave me some measure of contentment, because at least, I had a definable problem upon which I could blame the lengthy list of symptoms.
Dr. Penton prescribed dilantin, an anti-seizure medication, to calm the swell of flurries I felt in my head. I happily checked out of the hospital thinking that this new medication would prove to be the solution to my health crisis. Dr. Penton was not so optimistic.
Within a few hours of dismissal from the hospital, I was hallucinating and was gripped with unbearable pain. I suffered relentless terror as visions of wolves and demons uncontrollably plagued my mind. I tried desperately to communicate the anguish of my situation but only garbled babbling poured out of my mouth. The hallucinations became so ungovernable and the pain so excruciating that I began to beg the Lord to either end my dilemma immediately or translate me to heaven post haste. Despite my pleadings, there was no remission in the torment.
I knew my death was imminent when in my few lucid moments, I saw tears on the faces of my family as they bent over me and attempted to comfort me from the dreadful pain and as I heard the murmured whispers about the perilous state of my health. Little did they understand that death, at that moment, would have been a welcome relief.
As my conditioned worsened, I needed a catheter. The urine bag promptly filled with what appeared to be dark blood, not the bright red of fresh blood but rather like the color of dark dried blood on a ghastly wound. Some have described it as a port wine hue. The nurses, assuming that I was bleeding internally, ran from the room and tried to locate a doctor quickly.
As soon as Dr. Penton visually examined the sample, he suspected that the urine was colored by porphyrins not blood. If his hypothesis proved true, then it was almost certain that I had porphyria, a rare disease that had so intrigued Dr. Penton since he first studied the disease in medical school that he had watched for a case of porphyria for years and had never encountered one until mine.
Immediately, he ordered a 24-hour urine to establish the presence of a high accumulation of porphyrins and porphyrin precursors. We carefully kept the urine free from exposure to the light and made sure it was refrigerated. Upon completion of the test, the results were positive as Dr. Penton had suspected. Since further testing was needed to verify the diagnosis, Dr.Penton contacted the National Institutes of Health to perform the complicated blood tests to determine specific enzyme deficiencies that would, in turn, indicate the type of porphyria I had inherited.
While we waited for the results, my life remained on a precarious edge. Dr. Penton consulted with his colleague, Dr. Bruce Trippe, who joined him in the complex task of keeping me alive. Because certain drugs can precipitate a life-threatening attack of porphyria, both doctors were resolute in not treating my agonizing pain lest they worsen the situation. To further threaten my mortality, I developed an elevation in brain water content called "water intoxication" which also sincerely affected the central nervous system. Generally, at the level of "water intoxication" I was experiencing, convulsions, coma occur and death follows. I was, therefore, not allowed even a hint of fluid including anything as seemingly innocuous as a wet swab on my parched mouth. My thirst became as unbearable as the pain. I begged for water. I begged for pain medication. I begged to die. Most of the time, I could still only communicate my intended beggings with delirious babbling.
When the diagnosis of acute intermittent porphyria was finally established, steps were promptly taken to air-evacuate me to the National Institutes of Health (NIH), adjacent to our nation's capitol, where research was being conducted. Dr Penton's wife, Pat, who had been an intensive care nurse, donned her nurse's uniform and flew with me and my family on this most frightening journey of my young life. My only vivid memories of that trip are those of being placed by stretcher into the national guard airplane at our small Alabama airport surrounded by well-wishing friends, landing in a freezing ice storm and then being transported during that icy storm to NIH, our nations largest research facility.
Upon our arrival at the massive NIH institution, the physicians there warned my family that I was in critical condition and my chances of survival were minimal, particularly since my respiratory system was severely compromised. I was not privy to this information, so I blissfully supposed that I was now on the recovery road and could, therefore, dismiss my request to the Lord that He let me die quickly.
I was given experimental hemin infusions which brought me back to life within days. Today this treatment is commercially available as Panhematin, which was the first FDA approved orphan drug more than 25 years ago. I tell people that Panhematin may look a lot like swamp water or crank case oil, but it is PURE GOLD to me. Without it, my attacks were dreadful and often lasted many weeks.
"Remember.Research is the key to your cure!"
Andrew Turell and EPP Story #NPAW
Tuesday - April 14, 2015 @ 13:50:02
Andrew Turell
Type of Porphyria:
Erythropoietic Protoporphyria (EPP)
Andrew's Story
Although I was not diagnosed with porphyria until I was 10 years old, I have always suffered from the pain caused by spending too much time in the sun. As far back as I can remember beach vacations and summer camp were always linked with itching, burning and sleepless nights. Before I was able to verbally articulate the sensation, the only reason my parents believed that the pain was real was because I would continue to scratch my hands and face even once asleep (fortunately, I do not get blisters or other visible symptoms).
I visited a number of doctors and was tested for a variety of allergies, but nothing stopped the reactions. Every summer, I would inevitably experience a handful of painful reactions that would last between two and three days. Ice packs and cool wet towels were the only things that could alleviate the itching and burning. Unable to sleep, I would hole up in the basement because that was the coolest place in the house.
By chance my parents after one of my reactions, my parents were talking to an acquaintance who is a dermatologist. She diagnosed me on the spot without ever having seen me and suggested that I go to see Dr. Vincent Deleo. I did so, and he diagnosed me, put me on Lumitene and recommended certain sunscreens. Over time, I learned to take better care of myself and prevent reactions by reapplying copious amounts of sunscreen, wearing pants and long sleeves and avoiding sun exposure whenever possible. Even with all those precautions, I still continued to suffer a few reactions year.
Since I was a young kid, I have always loved baseball. Despite my EPP, I have continued playing and have recently started coaching as well. I wear long sleeved turtlenecks even on the hottest days of summer, and while playing baseball has caused the vast majority of my reactions, it has all been worth it.
Last year, I participated in the Afamelanotide trials at Mount. Sinai Hospital in New York. That summer, I spent more time outside than ever before and yet I did experience one bad reaction.
Currently, I am a student at the University of Pennsylvania where I am active in my fraternity, Psi Upsilon, and play on the club baseball team, eagerly awaiting the approval ofAfamelanotide by the FDA.
"Remember.Research is the key to your cure!"
#NPAW Story of Greg And Juliet Wilkerson PCT
Tuesday - April 14, 2015 @ 00:40:08
Gregs story, as written by his wife Juliet (caregiver)
My husband Greg is a literal mystery case. He has a laundry list of diseases that his docs at JohnsHopkinsUniversityHospitalcould not figure out. We relocated to Eastern Tennessee, and he continues to be a medical mystery. Today, I will share his porphyria (PCT) journey.
Greg and I lived on the Eastern Shore of Maryland for most of our lives. For many years, Greg had been having terrible outbreaks/rashes/etc on his arms, hands, and face. We saw our PCP frequently, and she kept giving Greg cream after cream after cream using reference books as a guide. He saw a dermatologist who biopsied a lump on his neck and said it was something hormonal. When we asked about his hands and forearms, he just gave him yet another cream! We were dumbfounded and perplexed and completely clueless at the time! Greg had been so sick with painful bumps and blisters, severely sunburned skin, general malaise and many other symptoms.
Greg and I have known each other since we were teenagers. I have always known him to be very sensitive to the sun. I have never known anyone to be so extremely uber sensitive to any stimuli to their skin. He cant even test his blood glucose on his fingers because it literally hurts/burns for days afterward. I have seen time, and time again when he gets out of the shower, his skin, (especially his back) is just beat red and very hot. Its the most bizarre thing I have ever seen!
In December of 2012, we moved to Eastern Tennessee and soon after, we started to line up Gregs new medical team. I ordered Gregs medical records, correlated them, and created a three ring binder book that I keep completely up-to-date. This way, his medical team has easy access to whatever records they may need. We also use the book ourselves as a learning tool so to speak.
The first new doc we met with was Gregs neurologist. He examined the terrible scars newly occurring blisters/bumps on Gregs hands and listened to the long history about his skin issues. He then sent Greg to a dermatologist who turned out to be one of our saving graces because she was finally able to tell us what was going on.
On Gregs first visit with the dermatologist, a biopsy was done on the raised blisters on his hands. This came back as granuloma annulare, another rare and odd skin condition. Greg had another painful and horrific break out and went immediately to see Dr. Anderson. She did another biopsy at that time. This came back as porphyria. The doc immediately set him up for blood work and urnine/fecal testing, which confirmed his porphyria (PCT) diagnoses. As soon as I heard the word porphyria I immediately went online to research this as I do with every condition Greg has. Thank God I found the American Porphyria Foundation. What an amazing resource and incredible help they have been!
Because Gregs dermatologist had never seen PCT and granuloma annulare occur at the same time, she invited us to come to a small dermatology conference at a colleagues office. They had several patients who where unusual cases that they wanted to review. We were glad to go.
At the conference, Greg was examined by a variety of medical professionals, who seemed to be very interested in his case. When these professionals sat down at their round table discussion, they all agreed, they had never ever seen granuloma annulare and porphryia (PCT) occur together. Once again, we were heart broken and lost. Greg is a zebra.
We were sent to a few other specialists who could not come to a consensus as to how to treat Greg. Plaquenil was on the table; however, the dosage each of them wanted to prescribe was not concurrent with what the American Porphyria Foundation recommends. We reached out to porphyria experts that we were able to actually chat with and correspond via email. Unfortunately, traveling to see them was not an option. Greg was not at all comfortable with taking the plaquenil either without a clear agreement as to the correct dosage. The rheumatologist we consulted with just seemed to compare treating a PCT patient like someone with lupus. We were hoping that we can get some clarity at some point about the proper amount that is safe and recommended for porphyria patients.
Or next consultation was with a hematologist/oncologist locally since we were not able to travel to meet with a physician who specialized in poyphyria. The hematologist did not recommend a treatment plan for Gregs porphyraia because he suffers from thrombocytopenia (low platelet count). When we mentioned plaquinel, the doc told us that we needed to go back to rheumatology. I kept telling all the docs we consulted that something was WRONG with my husband and that they were missing something critical! Finally, the hematologist ordered a CT Scan of Gregs lungs, and abdominal area. I think the doctor finally had an epiphany because of Gregs low platelet count and other very uncomfortable and painful symptoms. Sadly, the CT scan indicated cirrhosis of the liver. I immediately contacted the American Liver foundation and requested as much information as they could provide to us. We also learned that PCT and cirrhosis are linked. We felt that the he hematologist/oncologist suspected a liver issue that is perhaps caused by Gregs Porphyria Cutanea Tarda.
Greg was then sent to a gastroenterologist who also specialized in liver disease; he was diagnosed with Non-Alcoholic Stage IV Cirrhosis of the Liver (NASH). The doc also did extensive blood work and an endoscopy/colonoscopy to confirm the diagnoses. Because Greg has thrombocytopenia (low platelet count) he at this time, cant undergo a liver biopsy.
So we are left with so many questions. This bomb was basically just dropped in our lap as the doc walked out the door saying to us lose weight and stay off the carbs. We researched the liver diet and certain types of carbohydrates are a major portion of a liver diet.
Greg and I are exploring other options of care at this time. The GI doc did say that with diet and exercise, Gregs life could be extended. We are just broken, and beyond devastated. Greg and I are having a very difficult time trying to process all thats going on with him. At this time, this hour, this day, this minute, he does not need a liver transplant.
All of these blows just break our hearts. The problem is, with all of the other medical issues, his treatment options become more and more challenging and unclear. We believe that his PCT needs further investigation and a treatment plan. I feel like Greg has been tossed around like a hors-doeuvre tray at a cocktail party, time, and time again. We get no definitive answers Specialists we have seen all seem to have tunnel vision for the most part; at least in our experience.
As far as the PCT is concerned, we are very proactive. Greg must wear sunscreen when outdoors, long sleeve pants/shirts, along with UV wrap around hats that cover his face, ears, head, etc. He wears cotton gloves as well. We also try to check medications that are prescribed against those that are harmful to porphyria patients. I actually found a laundry rinse aide that you add to load of clothes called Sun-Guard by Rit that protects against UV Rays for up to 20 washings. Its recommended by the Skin Cancer Foundation as well. We try to plan our outings more towards the evening hours when the sun is not so extreme and hot. I make sure Greg gets plenty of rest as well. I watch over him very carefully 24/7.
We have found these things to be helpful. Be your own advocate. Leave no stone unturned; read, research, exchange ideas and reach out to others who suffer from porphyria. There are several groups on Facebook with wonderful people to chat with. Never ever be afraid to ask questions. Keep copies of all of your medical records. We are still on this journey and we continue to learn new things. The more knowledge you have, the better your care will be.
"Remember.Research is the key to your cure!"
Amanda Boston with VP
Monday - April 13, 2015 @ 14:21:58
Amanda Boston
Type of Porphyria:
Variegate Porphyria (VP)
I first saw the opportunity to participate in research studies on the American Porphyria Foundation (APF) Facebook Page. As soon I as I saw the post I knew I would love to volunteer! As a young woman in my twenties, I have a vested interest in the race for a cure, and the development of new treatments. Research studies even help document treatment options that are tried and true in some areas of the country but not others, which is a important in getting insurance companies to consider the treatments normal and standard and therefore a covered expense. This too is crucial in getting patients treatment.
I participated in three studies in 2014, the Longitudinal study, the Panhematin Study and the Anylam Study. The Longitudinal Study required no travel, just some lab work coordinated through my personal physician. The Panhematin Study involved traveling to the University of Texas Medical Branch (UTMB) in Galveston, TX. I stayed there five days participated in a double blind study to prove the effectiveness of the IV drug Panhematin. I already have this treatment available in my area and take it on a routine basis. However others are not so fortunate and the results of this study will help more people get the treatment prescribed and then covered by insurance. Then just last week, I went back to UTMB to begin participating in a study for a new drug through Alnylam. The study involved a physical exam and some lab work, which will be repeated twice more at six months intervals.
All my experiences at UTMB have been positive. Last week was no exception. I traveled that morning and arrived at 11am to meet Dr. Anderson, Dr. Ede, and Dr. Hallberg. Dr. Anderson is very knowledgeable and friendly and I was at ease instantly. I met him for the first time during the Panhematin study, and he knew what I needed from the moment I walked in. He had obviously read my medical records and understood Porphyria and understood the symptoms I was experiencing. He was quick to give me a Panhematin treatment at the onset of an attack and never put my health in jeopardy. This time I had a simple exam where they took my blood pressure, pulse, temperature, weight and height and then I gave a blood and urine sample. I flew home the next day, so it was a very small time commitment.
After the research was completed, I met with Desiree Lyon. She is one of the nicest people I have ever met. When she speaks about the foundation and research projects, you can truly feel the dedication and commitment. I admire her strength to cope with Acute Intermittent Porphyria herself while working so hard to help others. I met some other staff members as well who were friendly and took me out for dinner and made me feel at home and welcome. The next morning I had asked if I could see more of the work they do at the foundation, and I had the privilege of observing all morning until my flight that afternoon. I was impressed by the dedication and compassion of the staff!
I know that many people may hesitate to participate in research studies. I had reservations at first myself, and my fears were quickly put to ease. The time commitments have been small and the process has been all positive. I hope this article encourages you to become more involved and participate in finding a cure for Porphyria.
"Remember.Research is the key to your cure!"
Amy Rose Burke and PCt for #NPAW
Monday - April 13, 2015 @ 14:19:49
Amy Rose Burke
Type of Porphyria:
Porphyria Cutanea Tarda (PCT)
Amy Rose Burke
During the summer of 2009 I started having symptoms that were quite strange. I noticed my urine was a dark copper color and was experiencing some slight pain in my stomach. After visiting my family doctor a few times he decided to send me to an urologist to check for kidney stones. I had a CT scan and the doctor did not find any signs of kidney stones, however the test did show a spot on my liver, which he dismissed and told me not to worry about at this time.
After continuing to have problems with my urine, and having my doctor say, I dont know what you are eating or drinking to make your urine this color, I decided to try to drink more water and assumed it was just something quirky going on. A few short weeks later, I started to develop large water blisters on my fingers, on both hands. I also started to develop a strange rash on my forearms. I was quite embarrassed by the rash and I was constantly changing the band aids on my fingers. I even covered my arms with the tops of socks that I cut off to cover the rash. I went back to my family doctor and he prescribed an antibiotic and a topical steroid cream. After a couple more weeks, I called my doctor again and he decided that I needed to be seen by a dermatologist, immediately.
The visit to the dermatologist was more intense than I had expected. Fortunately I was being seen by a wonderful doctor by the name of Dara Spearman. She listened to my symptoms including the strange look of my urine and then she decided she would like to take a biopsy of one of the lesions on my arm. I asked her what she was looking for and she looked at my daughter and me and said, I think you have a disease called: Porphyria Cutanea Tarda. She said it is very rare and she doesnt see it very often. I was told to stay out of the sun, dont sit near windows, stay covered up and use sunscreen everyday. I walked out of her office with a full box of sample size sunscreen wondering, what in the world is going on! She also sent me to a lab for blood, urine, and stool tests. I was quite concerned when they said it had to be shipped off to the mayo clinic to be tested. She also had me checked for hepatitis. I immediately came home and started researching Porphyria, it sounded quite overwhelming, but the symptoms were matching up perfectly.
After a week of waiting, my diagnosis was confirmed to be familial PCT. My blood work also showed that I had had a bought with Hepatits B at one time. My liver enzymes were also extremely high.
The hardest part of getting things rolling with treatment was having a hematologist willing to take my case. My dermatologist told me I needed to start phlebotomy treatments as soon as possible. Her office tried to contact a hematologist to get things started; it took over 3 weeks before a doctor finally took the case. The first time I met with him he explained everything to me just as my dermatologist had; treatment would include phlebotomies and careful monitoring of my liver function, ect. He also admitted that he did not know a lot about the disease.
He set me up for my first treatment that very day, and it was terrible! My blood pressure dropped to 43/70 and I passed out and ended up getting the shakes terribly bad! I shook uncontrollably for about 20 minutes. They finally gave me some Dilaudid to settle me down. I was going in for treatments every four weeks and had the same reactions each time. Now my nurse gives me dalaudin and an IV first to calm me down. I am only 5 tall and weigh about 105 pounds, so I am only able to give a small amount of blood each time, maybe 4-6 ounces if Im lucky. About two months ago, I started developing the rash on my arms again, so my doctor has me going in every 3 weeks for the treatments. This summer has been rough dealing with staying out of the sun, ect. I used to love lying out by the pool, getting that great tan. I also love gardening and working in my flower beds. I have lost interest in a lot of those things, mainly because I know the sun is my enemy. I have adjusted to doing my yard work in the mornings or later in the evening.
Now, this probably sounds like a typical story for any Porphyria patient, however on top of this disease I also have multiple sclerosis, which I was diagnosed with about 4 years ago. I only had symptoms of numbness in my face when I was diagnosed. I was put on a medication called Rebif that I injected 3 times a week. This medication is supposed to help slow the development of the lesions on my brain which can cause further problems with my ms. The reason I mention the MS is because my doctor and I have come to the conclusion that the medication for the MS may have triggered the Porphyria and started to cause problems with my liver function. Thankfully there are different options for the treatment of MS, so now I am doing a daily injection and it seems to be working quite well and doesnt seem to be affecting my Porphyria. I wanted to mention this situation because I do believe that I had Porphyria all of my life, however certain diseases or medications may cause it to rear its ugly head!!
I am very thankful for my family and their support. My husband and daughter take turns going with me to my phlebotomys and have seen me at my worst, however they are always there to see me thru.
I am hopeful that thru my message, more people can understand how Porphyria can affect the lives of people who are living with it. I am also hopeful that although there is no cure for this disease that more research can be done to help everyone understand and deal with it better. No matter what type of Porphyria you have, we are all in this together and we can support and help each other thank you to the American Porphyria Foundation for helping us all connect with each other.
Porphyrins & Porphyria diagnosis
Saturday - April 11, 2015 @ 10:09:19
Porphyrins & Porphyria diagnosis
The porphyrias are caused by deficiencies of enzymes of the heme biosynthetic pathway. This pathway, like other chemical pathways in the body, is a sequence of steps leading to a final product, in this case heme. Heme is essential for life, and each enzyme is also essential, because it is responsible for one of the eight steps in making heme. Each porphyria is due to a deficiency but not a complete absence of one of the enzymes.
The porphyrias are caused by deficiencies of enzymes of the heme biosynthetic pathway. This pathway, like other chemical pathways in the body, is a sequence of steps leading to a final product, in
PORPHYRIAFOUNDATION.COM
#NationalPorphyriaAwarenessWeekâ?¬ â?ª#NPAW2015â?¬ has officially started!
Today we have 100's of people coming to the Shadow Ride Kick Off Event in Pawhuska Oklahoma to enjoy a Barbeque, with live music, fun games and a time to get to know one another. https://www.facebook.com/events/745826892205498/
Tomorrow we are Hosting a Patient Education Meeting in Oklahoma City, OK with porphyria expert, Dr. Sylvia Bottomley. The meeting will take place from 2-5 pm at the fantastic National Cowboy and Western Heritage Museum. https://www.facebook.com/events/1611698132408353/
It's time to Speak Up ~ Speak Out ~ Educate Share your Story ~ Get Involved.
Porphyria is not a single disease but a group of at least eight disorders that differ considerably from each other. A common feature in all porphyrias is the accumulation in the body of porphyrins or porphyrin precursors. Although these are normal body chemicals, they normally do not accumulate. Precisely which of these chemicals builds up depends on the type of porphyria.
The terms porphyrin and porphyria are derived from the Greek word porphyrus, meaning purple. Urine from some porphyria patients may be reddish in color due to the presence of excess porphyrins and related substances in the urine, and the urine may darken after exposure to light.
The symptoms and treatment vary significantly from one type of Porphyria to the next.
Porphyria symptoms arise mostly from effects on either the nervous system or the skin. Effects on the nervous system occur in the acute porphyrias (AIP, ADP, HCP and VP). Proper diagnosis is often delayed because the symptoms are nonspecific. Skin manifestations can include burning, blistering and scarring of sun-exposed areas.
The porphyrias are rare diseases. Taken together, all forms of porphyria afflict fewer than 200,000 people in the United States. Based on European studies, the prevalence of the most common porphyria, porphyria cutanea tarda (PCT), is 1 in 10,000, the most common acute porphyria, acute intermittent porphyria (AlP), is about 1 in 20,000, and the most common erythropoietic porphyria, erythropoietic protoporphyria (EPP), is estimated at 1 in 50,000 to 75,000. Congenital erythropoietic porphyria (CEP) is extremely rare with prevalence estimates of 1 in 1,000,000 or less. Only 6 cases of ALAD-deficiency porphyria (ADP) are documented.
EPP is the most common porphyria in childhood, and the one associated with the longest delays in diagnosis.
"Remember.Research is the key to your cure!"
Porphyria Research Consortium of the NIH Rare Disease **A must Read on updated Acute Porphyria testing**
Saturday - April 4, 2015 @ 10:30:00
MY AWARENSS PROJECT WAS TO HAVE SCIENTISTS DEVELOP A CLEAR DIAGNOSTIC ARTICLE FOR YOU .
The PORPHYRIA RESEARCH CONSORTIUM OF THE NIH RARE DISEASE CLINICAL NETWORK has created the following informational article for you and your physician. DIAGNOSTIC TESTING for the Acute Porphyrias- Clarification of Testing Results It has come to our attention that some patients who have been diagnosed clinically as having Acute Intermittent Porphyria (AIP) or another acute hepatic porphyria could not be confirmed by either biochemical or DNA testing. Biochemical testing is the demonstration of increased urinary ALA and PBG, and these values are highest during an acute attack when patients are symptomatic. Some patients can have high levels in between attacks as well, but not all. Positive diagnostic values should be increased greater than 5 times normal, not just a slight increase (less than 3 times normal) which can occur with dehydration. Most commercial laboratories and in particular the Porphyria Lab at the University of Texas Medical in Galveston which is run by Dr. Karl Anderson, will perform these tests properly. It is important that the doctor order urinary ALA and PBG and not a "porphyrin profile." DNA, or molecular genetic testing, for the acute porphyrias is performed by sequencing the causative gene for the three major acute porphyrias and finding a specific pathogenic lesion on the gene, called a mutation. The technique used for DNA testing is at least 98% accurate, and patients with significantly elevated PBG are most often found to have a specific mutation. In our experience of testing over 1000 patients with or without elevated urinary PBG, only a few cases did not have a specific mutation. For these patients, we undertake special testing to look for gene deletions or other aberrations that would be responsible for a cryptic mutation. During the last few years, our experience with DNA testing for the acute hepatic porphyrias has revealed certain mutations which are not pathogenic but are relatively frequent in normal individuals who do not have any acute hepatic porphyric symptoms. These are called polymorphisms and they are benign. When we recognize patients who have such polymorphisms, we continue to look further at their DNA to see if we can find a pathogenic mutation in addition. If no pathogenic mutation is found, we would have to classified or reclassify these patients as not affected. As you may be aware this has created great concern for patients who respond well to acute porphyria treatment that their treatment would be discontinued. We appreciate this concern and would like to have such patients physicians contact on us so that we can discuss their situation, recommend additional testing to determine if their symptoms may have been misdiagnosed and institute appropriate treatment. Diagnosing Acute Porphyria The acute porphyrias include Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and d-Aminolevulinic Acid Dehydratase Porphyria (ADP). AIP is the most common of the acute porphyrias. The most common symptoms are acute attacks of severe abdominal pain, back pain, pain in the arms and legs, nausea, vomiting, rapid heartbeat and other symptoms. These attacks generally last for several days, and can be sporadic or happen frequently (~once/month). These acute attacks are very rare in children before puberty. These acute attacks are very rare in children before puberty . Attacks are often provoked by certain drugs, alcohol, hormones, infections, and perhaps stress. HCP and especially VP may cause blistering skin photosensitvity, as well as acute attacks; AIP has no skin involvement, it is characterized just by these acute attacks. A diagnosis of one of the acute porphyrias is made in two ways: By biochemical testing: For AIP- a urine porphobilinogen (PBG) test during an acute attackthe urine PBG level will be very high if the symptoms are caused by an acute porphyria (greater than 5 times the normal value) For HCP and VP- a urine porphobilinogen (PBG) test during an acute attack if the patient has acute symp-toms, or plasma porphyrins if the patient has skin symptoms By genetic testing looking at the genes known to cause the acute porphyrias There are many misconceptions about the urine PBG testing, its reliability, and urine color of patients with acute porphyria. The urine sample for PBG testing needs to be protected from light; the sample should be wrapped in tin foil or placed in a brown opaque bag after collection. However, if the sample is exposed to light for a little while (a few minutes) this will not affect the results. Please follow the directions provided by the laboratory when doing this testing. Urine PBG testing can be sent to many labs including Quest, LabCorp, Mayo, ARUP, UTMB and Mount Sinai; they all do this testing reliably. Many patients have urine that is red/purple in color when they have an acute attack, but this is not always the case. Patients can still have elevated urine PBG levels even if their urine color is normal. These misconceptions may lead to improper testing, or misdiagnoses. Physicians who suspect a patient has an acute porphyria should call one of the expert Porphyria centers in the US to consult (http://www.rarediseasesnetwork.org/porphyrias/index.htm). The Difference between Active and Latent Acute Porphyria It is important to know that ~80% of people who have changes in their porphyria genes (called mutations) never have symptoms of the acute porphyrias. These people are said to have latent acute porphyria. If someone has a mutation in an acute porphyria gene and reports symptoms similar to an acute attack, their urine PBG level should be checked. If the urine PBG level is normal then there is likely another cause to this persons symptoms. Acute attacks are distinguished from other conditions that cause abdominal pain by very high PBG levels. Treatment of Acute Porphyria For patients with confirmed diagnoses, during acute attacks Panhematin infusions are administered as treatment and the pain is managed with various other medications. For more information on Panhematin please visit: http://www.aiporphyria.com/healthcare-professionals/â?¦/dosing If someone who does not have a confirmed diagnosis of acute porphyria, documented by very high PBG levels, is having symptoms that seem consistent with an acute porphyria attack Panhematin is administered at the discretion of the treating physician. Generally all other causes of abdominal pain which are much more common than acute porphyria are ruled-out first. If Panhematin is administered and subsequently the diagnosis of acute porphyria cannot be confirmed by elevated urine PBG values or DNA testing, then it would be concluded that the attack is not caused by an acute porphyria. Even after Panhematin treatment, or after an acute attack has passed, the urine PBG levels should still be elevated for several days to a week. These levels may not be as high as they were during the acute attack, but will still be elevated.
The Porphyrias Consortium aims to expand knowledge about the porphyrias and thereby benefit patients and their families. The Porphyrias Consortium enables a large scale collaborative effort to develop new strategies and methods for diagnosis, treatment, and prevention of illness and disability resulâ?¦
RAREDISEASESNETWORK.ORG
Robert Saupe' and EPP
Thursday - April 2, 2015 @ 10:30:00
Robert Saupe'
Type of Porphyria:
Erythropoietic Protoporphyria (EPP)
When Robert was a baby, his mom went to hang up clothes outside and put him on the grass so she could watch him. After a short time, Robert started screaming and crying. For years, Robert was tested for various allergies, including grass pollen, soap and various foods. When Robert was nine years old, his mom took him to see a doctor who had just completed an internship under Dr. James Kushner, an expert in porphyrias. The doctor looked at Roberts hands and face, suspected that he had porphyria and told him to make an appointment with Dr. Kushner.
Robert remembers going into the lab where Dr. Kushner did his testing. Dr. Kushner left the room, and when he came back he said, Bobby, you have porphyria. Dr. Kushner has called Robert Bobby ever since that day, and is the only person who calls him that. The nickname made Robert feel special. Dr. Kushner then kindly put a band-aid on Robert and wrote slugger on it, since Robert was starting baseball season.
Everyone in Roberts family provided blood samples to trace the origin of his erythropoietic protoporphyria (EPP). Robert was tested every six months and at 16 he gave a core sample to be tested for research.
Robert tried beta carotene, but the cost became prohibitive. Instead, he set out to build up a tan. He says that the more pigmentation he can get built into his skin, the better he can tolerate the sun. Unfortunately, building up the pigmentation can be terribly painful.
Although Robert had his gallbladder removed as a result of a buildup of porphyrins, he does not let his EPP keep him from living his life. He goes fishing early in the morning and works outdoors. Due to his excavation job, Robert has had to manage his EPP very carefully. He protects himself everywhere he goes by wearing leather gloves, wide-brim hats, 100% cotton shirts and bandanas over his face.
Robert works hard at photoprotection and copes with his EPP with humor. When a bystander saw Robert wearing a bandana at a NASCAR race, he asked if Robert had robbed a 7-11. Robert replied: shh, Im in hiding.
Robert is very excited about participating in the Afamelanotide trials in Salt Lake City. He recently reconnected with his 22 year old twins, who live in Salt Lake City. Robert says that years ago he was a bad character, but he gave his life to the lord and completely changed. Robert now talks to his children every day and enjoys hearing his son say, Love you, Dad. Robert has been saving for his trip and is looking forward to seeing his children.
"Remember.Research is the key to your cure!"
NPAW! What is it?
Wednesday - April 1, 2015 @ 10:30:01
National Porphyria Awareness Week 2015
National Porphyria Awareness Week (NPAW) April 11-18, 2015 is the week that the APF collaborates with YOU to enhance porphyria awareness in your communities. You can choose to initiate your own activity to promote awareness. Some of YOU have participated in health fairs, seminars, fundraising and media events. The APF will supply you with materials to make your awareness activity a success.
We also ask you to take every opportunity to spread the word about porphyria. Your effort can be as simple as purchasing an APF T-shirt or giving out medical information to your doctors or showing the APF Porphyria Live video to your family and friends. Every community needs to hear about porphyria, and you are the person to do that in your community. Please contact the APF for supplies.1.866.APF.3635
Speak Up ~ Speak Out ~ Educate Share Your Story ~ Get Involved
Get Involved ~ Join and Share the Event.
April 11-18, 2015 - National Porphyria Awareness Week. NPAW is the time we ask all people with porphyria to bring awareness to your own cities. NPAW has been very successful for the past ten years. Let's make this year the greatest! You can be involved in any way that works with your schedule, resources, and interests! Join the awareness movement in your local community! Together we can make a difference. Education and awareness are the first steps of treatment!
11 April 2015 - A Kick Off ride for the Shadow Ride on the famous Drummond and Hull ranches near Tulsa, Oklahoma in Pawhuska. There will be fun for everyone: live music, games, miniature donkeys to ride for the kids, the opportunity to meet other porphyria friends and Mary Hull's delicious Bar-B-QUE, plus, of course, The Shadow Ride TEAM.
12 April 2015 - Patient education meeting. Note the day following the Shadow Ride on April 12, 2015, the APF will host a patient education meeting in Oklahoma City, OK with porphyria expert, Dr. Sylvia Bottomley. The meeting will take place from 2-5 pm at the fantastic National Cowboy and Western Heritage Museum.
"Remember.Research is the key to your cure!"
date:
Apr 11 2015 - 12:01am to Apr 18 2015 - 11:59pm
BECOME AN APF MEMBER TODAY
Friday - March 20, 2015 @ 10:30:00
Get Involved
Click on the bold blue text below or on a topic listed on the left side of the page to read more.
Become a member of the American Porphyria Foundation today, and join us in our work for your good health!
When you join the APF, you become an integral part of an organization that empowers patients and helps them on the road to accurate diagnosis, proper care, and some day a cure. Adding your voice to ours makes us all stronger as we address our needs to health care providers, local, state and federal agencies and Congress.
Members of the American Porphyria Foundation receive:
Our quarterly newsletter news about porphyria research and clinical studies, scientific meetings and member get-togethers, and stories about the doctors working in the porphyria field and about members like you;
Attend APF Patient Educational meetings with Experts Nationwide;
Receive weekly E-News in your email;
Access to the APF In Touch network the ability to connect with others who share your diagnosis;
Free participation in telephone conference calls with top researchers in the porphyria field;
Knowledgethat you are an important part of keeping reliable medical information about porphyria available to those who are newly diagnosed, or at a crossroads in their porphyria treatment, and frightened;
And much more!
The American Porphyria Foundation relies on member support to sustain programs like this website and other literature written or approved by porphyria experts.
U.S. memberships are $35 annually; US membership suggested annual donation is $35. Donate and receive a FREE Porphyria Live DVD, as well as a number of pertinent brochures. International memberships are $45. The APF is a U.S. 501(c)(3) non-profit organization. All donations to the APF are tax deductible.
To join by phone with your VISA or MasterCard, call us toll-free at 1-866-APF-3635 Monday-Friday from 9:00 a.m. to 4:00 p.m. Central Time. To join by mail or fax, please click here to complete and print the donation form.
Unable to pay? Membership is free to all. The fee is only a suggested donation.
American Porphyria Foundation 4900 Woodway, Suite 780 Houston, TX 77056
Work with us!
The American Porphyria Foundation welcomes donations of your time and talents too. Would you like to volunteer or raise money for the APF, organize or attend an event, in addition to informing yourself about the porphyrias? If so, welcome! Youll find lots more information in this section of our website on opportunities to get involved in our, and you can always call our office for help: 1-713-266-9617.
The APF is here to serve, and were proud to have you with us.
"Remember.Research is the key to your cure!"
National Porphyria Awareness Week!
Monday - March 16, 2015 @ 15:44:31
National Porphyria Awareness Week!
National Porphyria Awareness Week (NPAW) is just around the corner, April 11-18! It is a very exciting time of the year. NPAW is the week that the APF collaborates with YOU to help you enhance porphyria awareness in your own communities and the medical professionals who practice there. Over the past years, some of YOU have participated in health fairs, seminars, fundraising and media events. Terri Witter, Amanda Boston, Marianna Donaghy, Amanda Rich, Stefanie Rehmann and many, many others have distributed Porphyria Fact Sheets, brochures and doctor packets to their physicians.
One of the important means to enhance awareness is to contact local media and ask them to run a story about you and your journey or your awareness event. This year's Shadow Ride is a good story, too, to use to draw attention to porphyria.
The APF will help you accomplish your own activity by providing materials including: Porphyria Brochures, A Porphyria Live DVDs, Fact sheets, Powerpoint Presentations and materials for medical seminars, as well as press releases for local newspapers and television and other suggestions. Even if you cannot organize an event, the materials are invaluable to mental health professionals, hospitals and all types of health organizations. Call us: 713.266.9617.
"Remember.Research is the key to your cure!"
Highlight of March: Story of Amanda Rich & AIP
Tuesday - March 10, 2015 @ 10:30:03
Hi my name is Amanda Rich.
I have acute Intermittent Porphyria or AIP. I found out in 2011 that I have it. Growing up I would have intense abdominal pain, joint pain, nausea, vomiting, mood irritability and always re week before and the week of my menstrual cycle. Now it makes sense. I ended up going to the e.r. with abdominal pain and I found out it was ischemic colitis. Well the medicine they gave me to treat it almost killed me. I then ended up in ICU for 9 days. While there I had to have a catheter place and the nurses started freaking because my urine was orange/purple. They didn't know what to do so I had my husband get my bio mom's autopsy report explaining AIP. The hospital then collected urine and sent it to the mayo clinic. Low and behold it came back positive for extremely high PBG levels and positive for AIP. I was referred to my local cancer center that has an AIP specialist. Fast forward to 2013, I had a port a cath place in my chest in July and everything seemed good. Or so I thought. My body rejected the port in August and I ended up becoming septic and was admitted to the hospital. Long story short I almost died 4 times that month. (the sepsis, anaphylaxis from mushrooms, kidney damage and renal failure from vancomycin, and then I got a DVT in my arm.) All while in hospital I was getting Panhematin, which was a lifesaver to curb my attacks. Then in Dec 2013 I volunteered for a research study and I went to nyc. I have also done other studies where they come to me and draw labs. I also just had my second port placed in august of 2014 and no problems yet. Despite it all I have a positive attitude due to my amazing family, friends and support team. Everyone that I have met through Facebook, the APF, and re groups have been there for us and we are grateful. Right now my two yr old is showing signs of AIP so we had her tested and she has the same mutation. I know now what to do for her. Thank you for reading my story and one day there will be a cure for all of us.
Thank You Amanda for sharing your story with us. IF you would like to share your story please email it to me @ Amy.apf@gmail.com
Do the following statements describe how you feel at times?
Im constantly thinking: What if . . . ? What if we get in a car accident? What if our plane goes down? Im anxious about things that a more rational person wouldnt worry so much about.Charles.
I feel anxious all the time, as though I were a hamster on a wheel running around but never getting anywhere. Im working myself to death but not really accomplishing anything!Anna.
When people tell me that Im fortunate that Im still in school, I say to myself, They have no idea how stressful school is!Daniel.
Im like a pressure cooker. Im always worried about the next thing that will happen or the next thing I need to do.Laura.
Fact of life: We live in what the Bible calls critical times hard to deal with. (2 Timothy 3:1) Because of that, anxiety can affect young people as much as it affects adults.
Is anxiety always bad?
The answer is no. In fact it is right for people to be anxious to please the ones they love.
Also, lets face itanxiety can be a powerful motivator. For example, suppose you will be taking a test at school next week. Anxiety might compel you to study this weekand that might help you get a better grade!
A degree of anxiety can also alert you to danger. You might feel anxious because you know that youre taking a wrong course of action and that you need to make changes for your conscience to be at rest, says a teenager named Serena.
Fact of life: Anxiety can work for youas long as it moves you to the right kind of action.
But what if anxiety traps you in a maze of negative thinking?
Anxiety might make you feel as if you were trapped in a maze, but someone with a different perspective can help you find a way out
Example: My mind races when I think about the different ways a stressful situation could turn out, says 19-year-old Richard. I play the situation over and over in my mind to the point that it makes me very anxious.
The Bible says that a calm heart gives life to the body. (Proverbs 14:30) On the other hand, anxiety can bring on a number of unpleasant physical symptoms, including headaches, dizziness, upset stomach, and heart palpitations.
What can you do if anxiety seems to be working against you rather than for you?
What you can do
Question the reasonableness of your anxiety. Being concerned about your responsibilities is one thing; being overly anxious is another. It reminds me of the saying, Anxiety is like a rocking chair. It gives you something to do, but it doesnt get you anywhere.Katherine.
What this means: Unless anxiety leads you toward a solution, it will only add to your problemor become your problem.
Take things one day at a time. Think it through. Will what you are anxious about matter tomorrow? in a month? in a year? in five years?Anthony.
What this means: It makes little sense to take on tomorrows problemssome of which may never even become a reality.
Learn to live with what you cannot change. The best you can do is prepare for situations to the extent possible, but accept the fact that some situations are out of your control.Robert.
What this means: Sometimes you cannot change your circumstances, but you can change the way you view them.
Put your situation in perspective. I find that I have to focus on the big picture and not stress over the details. I have to choose my battles and channel my energy into taking care of priorities.Alexis.
What this means: People who put their anxieties in perspective are less likely to be overwhelmed by them.
Talk to someone. When I was in the sixth grade, I would come home from school very anxious, dreading the next day. My mother and father would just listen to me as I expressed myself. It was so good to have them there. I could trust them and speak freely to them. It helped me to face the next day.Marilyn.
What this means: A parent or a friend might be able to give you practical suggestions on how to reduce your anxiety.
When Anxiety Is Severe
World RARE Disease Day
Tuesday - March 3, 2015 @ 23:34:31
Dear Global Genes Friends & Supporters,
We wanted to thank YOU for helping make World Rare Disease Day 2015 a huge success! Celebrated by patients, advocates, their friends and families, co-workers, caregivers, schools, doctors, nurses, biotech & pharmaceutical companies and rare disease foundationssupporters turned up and dressed down (in jeans, of course!) to spread awareness all over the world!
We would like to learn more about your World Rare Disease Day activities. In an effort to capture the highlights of all the events that happened around the world, please help us by responding to this survey. We would love to know how you celebrated and what you accomplished. We want to hear from you so we can share best practices with others, show the impact our awareness efforts made and ensure next year's World Rare Disease Day is the best ever!
Did you host or attend an event? Did your school or office participate in a Wear That You Care day? Did you hold a fundraiser? Whether you simply wore a ribbon or decked the halls in denim bluewe want to hear from you! Send us your pictures, stories and accomplishments for this years World Rare Disease Day using the link to the form below. Your story will be included in an upcoming RARE Recap post on the new RARE Daily!
Global Genes is a 501(c)(3) nonprofit organization advocating for rare disease globally.
If you would like to share what you did for this special day write us an email to Amy.APF@gmail.com
"Remember.Research is the key to your cure!"
Please read March's Highlight Story on Jackie Cory & EPP
Saturday - February 28, 2015 @ 08:07:08
Please read March's Highlight Story on Jackie Cory & EPP My name is Jackie Cory and I have Erythropoietic Protoporphyria (EPP). At a very early age I started complaining of extreme burning in my hands, knees, face, any exposed skin. I would cry & wail but no one understood. At 5 years old I remember being put in a bathtub full of ice & water. It helped but only for awhile. When I went to camp in 5th grade my hands swelled shut so I couldn't make a fist. I was so embarrassed & in pain. In junior high I couldn't do all the cool things my friends did like go berry picking or hang out at the beach. I was different & no one understood me. My parents took me to various Dr's but that only led to cortisone shots, allergy pills, special soaps & tranquilizers. I can still remember the awful taste of milk with atarax in it. I couldn't sleep, I would get up at night, run my hands under cold water then blow on them till they'd dry, then get up & do it again. I was always seeking shade, positioning my hands anyway I could to be hidden from the sun, in pockets, back to the sun, under my legs anywhere but in the sun. I could never explain it to anyone, after all my hands weren't red or hot to touch, must be in my head right? One day when I turned 35 I went to a dermatologist to see about getting some "tanning pills" I'd heard of. I thought since I'd never been able to tan this might help me stay out in it & feel "normal". He said it looked like I may have Erythropoietic Protoporphyria (EPP). He did a urine test & right there & then changed my life with a diagnosis. Now I had a real disease!!! All my suffering & pain was validated. At that time I had 2 boys aged 3 & 5, neither with any symptoms. I learned of sun protective clothing & uva/uvb sunscreen. Luckily at this age I didn't care if I was a "sun nerd" with big hats, gloves, long sleeves I now had a real disease! Learning of the American Porphyria Foundation was another huge plus. I could actually read about other people like me! A few years ago I participated in the clinical trials for Scenesse in San Francisco & on one occasion actually got to talk with 2 men that also had EPP. It had been my life-long dream to actually meet someone else who had endured this monster. Thank you APF!!!! I am now 62 with a loving husband, two grown boys & a wonderful grandson that all love & accept me for who I am, "sun nerd" and all.
I would just like to mention that my brother also has a rare genetic disease, Alpha 1 Antitrypsan Deficiency. We had an older sister who was born with sclerosis of the liver & died at age 5 due to it. We'll never know which genetic disease contributed to that but wow, how rare to have 3 children, all with a rare, unknown disease back in the 50's. Thanks so much for taking the time to read this. Knowing that other people understand and care means so much
Jackie Cory If you would like to share your story please email me at Amy.apf@gmail.com. Many can learn from you! Please share.
"Remember.Research is the key to your cure!"
Celebrate Rare Disease Day With Us! TODAY!
Monday - February 23, 2015 @ 17:09:10
Celebrate Rare Disease Day With Us!
Rare Disease Day takes place on the last day of February each year. The main objective of Rare Disease Day is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients' lives.
The campaign targets primarily the general public and also seeks to raise awareness amongst policy makers, public authorities, industry representatives, researchers, health professionals and anyone who has a genuine interest in rare diseases. It is the date to raise porphyria awareness!
Since Rare Disease Day was first launched by EURORDIS and its Council of National Alliances in 2008, thousands of events have taken place throughout the world reaching hundreds of thousands of people and resulting in a great deal of media coverage.
The political momentum resulting from Rare Disease Day also serves advocacy purposes. It has notably contributed to the advancement of national plans and policies for rare diseases in a number of countries.
Even though the campaign started as a European event, it has progressively become a world phenomenon, with the USA joining in 2009, and participation in a record-breaking 84 countries around the world in 2014. We hope many more will join in 2015. Some countries have decided to raise rare disease awareness further, for example, Spain declared 2013 as the National Year for Rare Diseases.
On rarediseaseday.org you can find information about the thousands of events happening around the world to build awareness for people living with a rare disease and their families. Promote the knowledge about porphyria in your communities!
Shadow Ride Updates
We will reserve the bed and breakfast inPawhuska, OK for Friday, April 10 and Saturday, April 11 for The Shadow Ride. Please call us to confirm and RSVP your spot.
You can stay in nearby Bartlesville or drive on to Oklahoma City that evening in preparation for the Patient Education meeting with renowned expert, Dr. Sylvia Bottomley. We have a list of hotels and detailed map ready for you!
As you already know, the Kick Off ride will be held on April 11, 2015 on the famous Drummond and Hull ranches near Tulsa, Oklahoma. There will be fun for everyone, including games and miniature donkeys to ride for the kids, as well as The Shadow Ride, the opportunity to meet other porphyria friends, try Mary Hull's delicious Bar-B-QUE and watch a cowboy show. The following day, the APF will also hold a patient education meeting at the famed Cowboy Museum on April 12, 2015 from 2-5 pm. Dr. Sylvia Bottomley will make a presentation on the porphyrias and answer your questions.
Save the date, come casual and be prepared to have a wonderful time!
Please contact the APF at 713.266.9617 for maps and hotels, details of the ride and to RSVP. Everyone is welcome!
"Remember.Research is the key to your cure!"
Thought for the week Please read and share
Monday - February 23, 2015 @ 17:05:19
Support & Purchase APF for Awareness Week 100% goes back to APF
Thursday - February 19, 2015 @ 11:29:46
New APF Stuff is here gets yours today before they go! All Pictures included below
New APF Long Sleeve & Short Sleeve APF T-Shirts are here!
â?¢ Short Sleeve White/Purple Lettering
â?¢ Long Sleeve are Dark Grey w/ Purple Lettering
Our hope for the T-shirts is that you all will buy and wear them to help promote and raise questions about Porphyria and to raise funds for the Dr. Packets, pain Management docs, among many other publications we make available at no cost. There are also some copies of Porphyria Live for sale. For information on how to order the T-Shirts and/or the Porphyria Live Video see below.
You can order a T-shirt and/or Porphyria Live DVD, Awareness Ribbons & Wristbands by sending an email order to Amy.APF@gmail.com.
I must have name, complete address, and phone number. Also include the Quantity of T-shirts and the size for each one.
To accept payment: One of two options: 1} I can accept Paypal VISA/MC only I must have full name on the card, account#, exp. date, 3 digit code on back of card CVV-
2}I will accept money orders. You must have name/address/phone # on them. Your information will be kept confidential and never on file, and will be destroyed promptly after each transaction. Address will be supplied after order is received for privacy purposes.
*The APF will not take orders or calls about T-shirts*
Once I receive the order I will ship out your product. All products will be shipped out Priority mail with tracking. Each person also will receive a receipt with T-shirts. T-shirts come in the following sizes S, M, L XL,1xl, 2xl, 3xl they are 100% cotton, heavy not thin, and very durable. No other sizes. The price per T-shirts is 19.00$/shirt. Long sleeve shirts are priced at 25.00$/shirt. This covers the shirt, shipping and tracking, and priority mail. International orders: I will have to consult first with the post office for shipping rates.
The price of the Porphyria Live DVD is $10.00 each. Shipping is included in the price. See porphyriafoundation.org for content info. ****We now are selling Porphyria Awareness Ribbons****
We have Dark Red, Dark Purple, Royal Blue, Mixed Red/Purple they each come with a pin on the back. Each are 2.00$ each or 4/8.00$
- Please specify what color you are wanting or I will give assortment per order. If purchasing another APF items there is no extra charge for shipping.
Dont forget we also have the APF wristbands to match in the same colors as the ribbons. Please specify what color you are wanting or I will give assortment per order. Shipping is 6.00$ for all the wristbands. Cost for wristbands is 2/6.00$ or 3.00$ each
100% of all funds received will go back to the APF
"Remember.Research is the key to your cure!"
If Finn Can Promote Porphyria Awareness, You Can Too!
Sunday - February 15, 2015 @ 13:09:24
If Finn Can Promote Porphyria Awareness, You Can Too!
Finnian, nicknamed Finn, can show us a thing or two about promoting porphyria awareness. He wears his American Porphyria Foundation bandana proudly. The APF gave bandanas to all the pets, who entered the APF Pet Beauty Contest a few years ago. Finn is a 7 year old yellow lab. His mom is APF member, Kelsey Castro who says of Finn:
He is my best buddy! He is always by my side, especially when I'm not feeling well I think he can sense it. I got him when I was 14 and in high school, and I'm now in college. Finn has been my best friend through lots of hard times. His favorite thing to do is go on hikes at a local nature reserve by my house and curling up by our wood stove in the winter.
We also ask you to take every opportunity to spread the word about porphyria. Your effort can be as simple as purchasing an APF T-shirt or giving out medical information to your doctors or showing the APF Porphyria Live video to your family and friends. Every community needs to hear about porphyria, and you are the person to do that in your community. Please contact the APF for supplies 713.266.9617.
"Remember. Research is the key to your cure!"
World Rare Disease Day 2/19/15 Share. Be apart of this because YOU ARE RARE!
Sunday - February 8, 2015 @ 23:05:52
World Rare Disease Day is an annual observance to raise awareness for rare diseases, and improve access to treatments and medical representation for individuals with rare diseases and their families. Created by European organization EURORDISin 2008, this day is celebrated on the last day of February each year. The 8th annual World Rare Disease Day will be held on Saturday, February 28, 2015. On this day, various activities take place globally.
Looking for ways to get involved?
Global Genesâ?¢ holds a variety of awareness raising activities starting on World Rare Disease Day and continuing throughout the month of March (because RARE deserves more than a day). Please join patients, families, friends, caregivers, scientists, physicians, researchers, health care providers, policy experts and our team to raise RARE disease awareness. Here are a few ways you can get involved!
February/March Events for Rare Disease Awareness â?¢ Tweet Chat in Partnership withWEGO Health Focusing on community events and facts & stats surrounding World Rare Disease Day. Thursday, February 19 at 2PM EST, participants can log on to Twitter and follow hashtags #RARETalk and #hachat to share ideas and win Global Genes & Wego Health swag bags, Walgreens gift cards, and more!
â?¢ Global Genes 1st Annual Denim Dash Virtual 5k Run/Walk for Rare Disease (Virtual/Global) March 21-29, 2015 The Denim Dash was created through collaborative efforts between Orphan Drug Solutions and Global Genes as their first annual virtual 5K event. This virtual 5k is designed to ensure that anyone, anywhere, can participate and show their support and raise awareness for patients, family and friends of the Rare Disease Community. The cost to register is $35 and includes Denim Dash t-shirt, race bib and Blue Denim Genes Ribbon. In order to receive a t-shirt, registration must be completed by 3/6/2015. Register here.
â?¢ Give RARE (Online) Give RARE, on March 3rd, is a single day for the world to GIVE to RARE disease! In partnership withZenzaga, the Give RARE technology platform allows rare disease nonprofits to sign-up easily to create a donation page, raise funds for their cause and get access to win prize funds from sponsors. Grants will be given throughout the day. Register by February 15th and your nonprofit will have a chance to win a year's worth of URS charity filings (worth $5000) from launch partners Charity Compliance. Register your cause today!
â?¢ 'I Love Someone RARE & Beautiful.' T-shirts in Partnership with the Gwendolyn Strong Foundation Global Genes and the Gwendolyn Strong Foundation have partnered once again by bringing back the popular 'I love someone RARE & beautiful.' tee in celebration of World Rare Disease Day. This is a LIMITED EDITION item, so get them while they last! They can be purchased here.
â?¢ Wear That You Careâ?¢ campaign - All across the world people participate in supporting rare disease awareness andWear That You Care by wearing the Blue Denim Genes Ribbonâ?¢ and their favorite pair of jeans on World Rare Disease Day. Wear That You Care campaigns take place locallysupporters often urge their offices, teams or other groups to wear jeans on a specific day and make a donation.
â?¢ Social Media Awareness - Patients, advocates, and industry alike can grow social awareness by sharing photos, information, and events with Global Genes' Facebook, Twitter, and Instagram. Where supporters can tag their photos or posts with hashtags #WearThatYouCare, #WRDD2015, #RAREadvocate, and #CareAboutRare to help draw attention to their content. Additionally, supporters can visit www.globalgenes.org/CareAboutRare and upload their photo into photo frames to use as social media profile images to further help spread awareness.
Join the movement! Advocate for the over 350 million with a RARE disease today!
Global Genes is a 501(c)(3) nonprofit organization advocating for rare disease globally.
National Porphyria Awareness Week is Coming Up!
Monday - February 2, 2015 @ 16:29:29
National Porphyria Awareness Week is Coming Up!
Our APF members set a great example of different activities that increase awareness in their local communities. Let's continue the tradition! In preparation for NPAW, April 11-18, 2015, the APF will send you a packet with brochures, a complimentary DVD and extra materials if you would like to distribute information in your area.
NPAW is the time we ask all people with porphyria to bring awareness to your own cities. NPAW has been very successful for the past ten years. Let's make this year the greatest! The Shadow Ride event and patient meeting in Oklahoma City, OK will be the Kick Off. We will post suggestions for what you can do on our Facebook pages and in E-news. Please let us know your address or call the APF office and get involved: 866.APF.3635.
You can be involved in any way that works with your schedule, resources, and interests! Join the awareness movement in your local community! Together we can make a difference. Education and awareness are the first steps of treatment!
Fresh Newsletter
Our quarterly Newsletter is almost done! It contains all the latest news from the porphyria world, experiences of our members and newest announcements. The APF is able to maintain our Newsletter, physician and patient education programs and many other services because of your support. Since we do not receive government funding, we need your support and donations. We also need your new contact information if you have a new address or email.
Please share your ideas with us.
"Remember. Research is the key to your cure!"
The Doctor- Patient RELATIONSHIP
Thursday - January 29, 2015 @ 15:44:41
When facing Porphyria disease, your Doctor his/her team and the partnership formed among everyone involved are keys to a positive experience and the best chance of a good outcome. In a patient, and family-centered care approach, your doctor provides an open and trusting atmosphere where you and your family can tell your story, share what is important to you, express your concerns and worries; learn about your diagnosis and treatment options; and work together on making decisions about your care that fit your values, life situation and goals. It is also finding humor when possible; chatting about everyday things; celebrating successes and sharing sad times if facing difficult times. In this relationship you feel respected and valued as a person and feel empowered to take an active role in your care and any decisions affecting you. If you and your loved ones, have this kind of relationship with your doctor and team, you will have a positive experience, but you might ask how this partnership with your doctor and team help your chances of getting the safest and best care to support your treatment and life goals. Please stay tuned for helpful hints in the next blog
"Remember..Research is the key to your cure!"
A Poem By Georgina Davis
Monday - January 26, 2015 @ 17:37:05
Georgina Davis, who is a member of the APF EPP Facebook Group, lives north of London in Hemel Hempstead Hertfordshire. She is a very creative woman, who is quite adept at drawing, painting portraits, most crafts and writing poetry, which she began 25 years ago, after a bad bout of her other disease, Multiple Sclerosis. Georgina writes poetry to express her feelings and help others understand her EPP. She says that the Facebook groups were a Godsend for her and has thanked the APF for its efforts to promote understanding of the porphyrias to doctors and the general public and most of all for bringing porphyria people together to reduce the loneliness. Look at the lucky people having fun. If we dare to fit in, They can go out in the sun, My oh my, watch out for the pain to begin. Scantily clad in the heat of the day. The slightest exposure can cause such pain If we did that, oh how wed pay. That we dont want to go out again. But, we are rare, not many like us, Feeling as though our bloods on the boil, Who when the sun comes out, And, lack of understanding for all our toil. We make a fuss. Swelling and itching all part of the course, We have a genetic condition you see, When into the sun we are forced. And it goes by the name of, With large floppy hats, long sleeves and gloves, Erythropoietic Protporphyria aka EPP. Covered all up from our heads to our toes. Isolation is its game, What a funny sight to see, While others play and have fun, People like us who suffer from EPP. We hide indoors away from the sun. If you have a talent to use for porphyria, please contact the APF. 1-866-APF-3635
"Remember..Research is the key to your cure!"
Here are some videos on You Tube about Porphyria.
Monday - January 19, 2015 @ 10:30:00
Here are some videos on You Tube about Porphyria.
Here are some videos to understanding- What is Porphyria? How it can be treated, how Panhematin is prepared, and Expert Doctors explanations and personal stories.
Think Porphyria
An Expert Opinion
How to Prepare and Admin Panhematin Lindsey
Desiree Lyon APF
Amy Chapman AIP
John Chamberlayne VP
Dr. Lisa Kerberg AIP
British Porphyria Association - Sue Burell AIP
Adrian EPP
Tracey Yelen AIP
Please visit porphyriafoundation.org/ 1-866-APF-3635 to receive any information for you and your medical team. It could save your life.
"Remember..Research is the key to your cure!"
PORPHYRIA DOCTOR FINDER
Thursday - January 15, 2015 @ 10:30:01
PORPHYRIA DOCTOR FINDER
Every day the APF receives requests for a doctor who can diagnose and treat porphyria. The main question we hear is, Where can I find a doctor to treat me? In the past, the APF has only given out the names of doctors who were experts in the porphyrias, but the number of experts is very small. However, our policy has changed a bit since there are now 5000 members and so few experts. Many of our members have told us that their doctor has some measure of knowledge about the porphyrias and that their doctors diagnosed and treated them well. A few years ago, we began to collect the names of those doctors around the country and placed them on our database. We also sent out several thousand very comprehensive Physician Education packets to doctors who were interested in learning about porphyria. At the behest of many of you, we created FIND A DOCTOR section on the APF website. Check the FIND A DOCTOR section and see if a city near you is listed. Then call the APF for the doctors contact information. Watch the website often as the section will be updated often. Experts are also listed for an appointment. If you have a great doctor, please contact the APF. (1-866-APF-3635) ****Note we cannot validate the level of knowledge of any of the listed doctors other than the porphyria experts. See porphyriafoundation.com.
"Remember..Research is the key to your cure!"
A LITTLE BIT OF HISTORY
Tuesday - January 13, 2015 @ 17:30:11
A LITTLE BIT OF HISTORY
Porphyria began at the beginning of time and has continued to mutate throughout ensuing generations. The name "porphyria" is only rather recent. For centuries it was known as a blood/liver disease. At one time the abdominal pain was actually thought to be from the liver. The term porphyria itself is derived from the Greek Ï?οÏ?Ï?Ï?Ï?α, porphyra, meaning "purple pigment." The name is likely to have been a reference to the purple discoloration of feces and urine when exposed to light in patients during an attack. Although original descriptions are attributed to Hippocrates, the disease was first explained biochemically by Felix Hoppe-Seyler in 1871 and acute porphyrias were described by the Dutch physician Barend Stokvis in 1889. Before, in 1844, Gerardus Johannes Mulder determined the chemical composition of this purplish, iron free substance, which he named "hematin." He also illustrated that hematin took up oxygen. Later, in 1867, J.L.W. Thudichum described the spectrum and fluorescence of these red porphyrins after he published his first book on the analysis of urine. Based on that, in 1871, Felix Hoppe-Seyler (photo L) crystallized hematin and described its spectrum. He then demonstrated that the crystalline form differed from one animal species to another. Using his own newly constructed gas pump, he found that oxygen formed a loose, dissociable compound with hemoglobin, which he called "oxyhemoglobin." He renamed the iron free hematin hematoPorphyrin. He is a German physician known for his work in establishing biochemistry as an academic discipline. Felix was the first to obtain lecithin in a pure form and introduced the word proteid (now protein). Additional contributions included metabolic studies and researches on chlorophyll and blood, and especially abovementioned hemoglobin, which he obtained in crystalline form. In 1874 - Dr. J.H. Schultz first described a case of a 33-year-old male weaver who suffered from skin sensitivity, an enlarged spleen and reddish urine from infancy. He called the condition pempigus leprosus. His was most likely the first description of protoporphyria (EPP). Dr. Schultz was later credited with giving the disease its name.In 1880 MacMunn described a patients dark reddish urine during an attack of acute Porphyria. Shortly after in 1888, sulphonal was introduced as a hypnotic drug, Joseph Stokvis (photo L) had a patient, who, after taking the drug, excreated the tell-tale dark reddish urine typical of porphyria. The elderly woman then became paralyzed and died. Stokvis deducted that the pigment in her urine was the hematoporphyrin. Based on that experience, in 1889 B. J. Stokvis published the first case and clinical description of acute hepatic porphyria. CEP porphyria was identified in the year 1923. In 1930, Hans Fischer (photo R), the Nobel laureate, described heme as the compound that makes blood red and grass green. By 1937 Dr. Waldenstrom in Sweden published his findings. For a time AIP was known as Swedish porphyria, or Waldenstrom's porphyria. In the 1960's porphyria research began in earnest in Europe and in the US. The big break came when scientists were able to recognize ALA and PBG in the 60's. Overall, by the 1960s, all known types of porphyria had been identified and environmental factors were shown to affect the disease course. Research in the 1980s and 1990s led to the identification of the molecular defects in each type of porphyria.
"Remember..Research is the key to your cure!"
CARBOHYDRATES IN ACUTE PORPHYRIAS~
Tuesday - January 6, 2015 @ 13:44:51
CARBOHYDRATES IN ACUTE PORPHYRIAS~ For some individuals, who have the "acute porphyrias" (AIP, VP, HCP and ALAD), attacks can be brought on if carbohydrates and calories are restricted for prolonged periods of time. For example, during the Atkins diet craze, many people with porphyria were diagnosed when their reduction of carbohydrates precipitated attacks. This is why fasting or major dieting is not recommended. Thus, to prevent and treat attacks, carefully monitoring ones diet can be especially important for these types of porphyria. Why are these three porphyrias more sensitive to diet? The pathway in the liver that makes heme from porphyrins and other substances is very sensitive to carbohydrates in particular. Therefore, when less carbohydrate is taken, it appears that porphyrin production is stimulated, and the body can't use them all effectively. This porphyrin overflow is what creates the symptoms of an attack. Carbohydrates are the foods that contain starches or sugars. They are important in everyone's diet, because they provide us with fuel for our bodies, as well as a wide variety of vitamins and minerals in many of the carbohydrates. Starches are "complex carbohydrates" (l) and tend not to be as sweet as sugars. Starches are called "complex" because they are larger molecules and take longer (compared to sugars) for our bodies to break them down for use as an energy source. Some starchy types of foods include: potatoes, pasta and bread. Sugars are "simple carbohydrates, (l) meaning their molecules are not that big and are quickly broken down in the body. They are quickly absorbed into our bodies as an energy source. These sugars may be found naturally in foods, such as fruit, fruit juice, some vegetables, and milk and milk products. Sugars are also found in higher levels in foods like honey, table sugar, candy, syrups and regular soda pop. Note that this last group of foods, although high in sugar, lack vitamins, minerals and fiber. Starches and sugars eventually break down into a substance called glucose, which is used as fuel by the body. When carbohydrates are broken down into glucose in the body, it may help minimize the over-production of porphyrins in the liver. Because this seems to be such a simple treatment, it is not adhered to by some who dont understand that this simple treatment involves a very complex mechanism. The guidelines suggest that when a person is having symptoms of porphyria, the carbohydrate intake be increased. In fact, some people help prevent attacks by maintaining a high carbohydrate intake daily.
"Remember..Research is the key to your cure!"
The Reason for the Shadow Ride
Friday - January 2, 2015 @ 21:44:31
The Reason for the Shadow Ride
A Cowboy Love Story What better story than a cowboy love story? And this love story is the REASON for the Shadow Ride.
Cowboy, Scott MacMeeken fell in love and married his beautiful bride, Michelle. All was great except Michelle has Erythropoietic Protoporphyria (EPP). Since Scott couldnt change her EPP, he conceived of the Shadow Ride, a horseback adventure to enhance awareness about porphyria across the small and big cities of America and to ask all of you to join them along the way. The Shadow Ride is a horseback ride that will eventually track across the American Discovery Trail starting in 2016, but the 2015 Kick Off ride will be held in Oklahoma near Tulsa, on the prominent Hull and Drummond ranches and will be followed by a national patient meeting in Oklahoma City in April, 2015. Soon thereafter, we will host a patient education meeting in Oklahoma City with renowned porphyria expert, Dr. Sylvia Bottomley. She will be making a presentation about porphyria and answering your questions at the Patient Meeting. Dr. Bottomley has been a major force in the pophyrias for decades. In fact, she wrote the most recent porphyria chapter in the prestigious Winthrops Medical Textbook. Dr. Bottomley can be seen, too, in the Porphyria Live DVD, that can be purchased on the APF website or received free with each donation. Attending a Patient Education Meeting is a great way to learn from and teach others with porphyria.
You will receive a notice with all the details of the ride and the National Patient Meeting. With a $30 donation to the APF, you can purchase a Shadow Ride T-Shirts with above logo. See at theshadowride.com
Contact the APF to order your T-Shirts with a $30.00 donation. Your donations will support the physician education program. Drag out your cowboy hats and boots and join the Partner Round Up. If you are willing to help with the Oklahoma City meeting or the Kick Off ride, please contact the APF.
Recordati Rare Diseases, the groups American subsidiary offers a portfolio of products for the treatment
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When Robert was a baby, his mom went to hang up clothes outside and put him on the grass so she could watch him. After a short time, Robert started screaming and crying. For years, Robert was tested for various allergies, including grass pollen, soap and various foods. When Robert was nine years old, his mom took him to see a doctor who had just completed an internship under Dr. James Kushner, an expert in porphyrias. The doctor looked at Roberts hands and face, suspected that he had porphyria and told him to make an appointment with Dr. Kushner..jpg)
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Cowboy, Scott MacMeeken fell in love and married his beautiful bride, Michelle. All was great except Michelle has Erythropoietic Protoporphyria (EPP). Since Scott couldnt change her EPP, he conceived of the Shadow Ride, a horseback adventure to enhance awareness about porphyria across the small and big cities of America and to ask all of you to join them along the way. The Shadow Ride is a horseback ride that will eventually track across the American Discovery Trail starting in 2016, but the 2015 Kick Off ride will be held in Oklahoma near Tulsa, on the prominent Hull and Drummond ranches and will be followed by a national patient meeting in Oklahoma City in April, 2015. Soon thereafter, we will host a patient education meeting in Oklahoma City with renowned porphyria expert, Dr. Sylvia Bottomley. She will be making a presentation about porphyria and answering your questions at the Patient Meeting. Dr. Bottomley has been a major force in the pophyrias for decades. In fact, she wrote the most recent porphyria chapter in the prestigious Winthrops Medical Textbook. Dr. Bottomley can be seen, too, in the Porphyria Live DVD, that can be purchased on the APF website or received free with each donation. Attending a Patient Education Meeting is a great way to learn from and teach others with porphyria.