Diagnosis and Testing

Diagnosis of the Porphyrias

First-line Testing for the Acute Porphyrias

Table 1. First-line Testing for Patients in Whom Acute Porphyria is Suspected

*Take sample when symptoms are present

Acute porphyrias

An acute porphyria should be suspected if patient presents with neurolvisceral signs and symptoms. The first-line screening test is measurement of urinary porphobilinogen (PBG). PBG is markedly increased in all patients during acute porphyria attacks and not markedly elevated in other medical conditions that can present with similar symptoms. Therefore, this test is both sensitive and specific for diagnosing an acute porphyria. An exception is ADP, in which ALA is elevated but not PBG. However, the condition is not usually under consideration because of its extreme rarity.

Measurement of PBG is often combined with ALA and total urine porphyrins. In some patients with acute porphyria, urinary porphyrins may remain increased longer than ALA and PBG. However, mild increases in urinary porphyrins can occur in other medical conditions and is therefore much less specific than increases in ALA and PBG. In urgent situations, a “stat” PBG for diagnosis is not available through any of the large reference labs. While the report is pending, initial management of the patient should be tailored to the possibility of acute porphyria, correcting fluid and electrolyte imbalances, pain control, and avoidance of medications that could worsen an attack (such as phenytoin for seizures). Patients with progressive neurological signs should be started on intravenous hemin. Intravenous dextrose can be administered while hemin is being prepared but should not cause a delay of hemin infusion.

If urine ALA and PBG are normal during an attack, it essentially rules out an acute porphyria. If urine ALA and PBG are markedly increased, a diagnosis of an acute porphyria is confirmed and further testing is needed to identify the type of acute porphyria. A minor (~2-fold) elevation in urine porphyrins (especially coproporphyrin) with normal ALA and PBG is nonspecific and may not require further testing.

Table 2. Second-line Biochemical Testing for Acute Porphyrias: Laboratory Findings to Differentiate Between AIP, HCP and VP.

Labs that can be used for second-line testing include: UTMB, ARUP, Mayo, Quest, and LabCorp

Cutaneous porphyrias

The screening tests vary by specific symptoms for the cutaneous porphyrias. Total plasma porphyrins should be done for blistering skin photosensitivity. If this test is normal, cutaneous porphyrias that cause blistering skin lesions are effectively excluded. Further testing may be needed if total plasma porphyrins are increased. For suspected EPP/XLP, which has non-blistering photosensitivity, an erythrocyte protoporphyrin test is more specific. Urine ALA and PBG testing is not informative for any of the cutaneous porphyrias.

Table 3. Testing for Cutaneous Porphyrias: Laboratory Findings to Differentiate Between CEP, PCT, and EPP/XLP

For all the porphyrias genetic testing is recommended to confirm the diagnosis as well as biochemical testing. The following table lists the causative genes for each type of porphyria.

Table 4 Genes Responsible for the Porphyrias

**The Mount Sinai Lab only tests for urine ALA and PBG

Diagnostic Testing Laboratories

Biochemical Testing Laboratories:

The laboratories listed with a ** are overseen by a Porphyria expert who can consult with the referring physician about test results.

UTMB Testing Packet/Order Form

ARUP Laboratories**
University of Utah
500 Chipeta Way
Salt Lake City, UT 84108
(801) 583-2787

Quest Diagnostics
33608 Ortega Highway
San Juan Capistrano, CA 92690
(866) 697-8378

Mayo Clinic
Biochemical Genetics Laboratory
200 First Street SW
Rochester, MN 55905
Tel: (800) 533-1710 or (507) 266-2888
Fax: (507) 266-2888

Sema4
62 Southfield Ave
Stamford, CT 06902

Contact Information:
clientservices@sema4.com
Tel: 800-298-6470
Fax: 646-859-6870

Sema4 General Test Requisition

At present Labcorp, ARUP, & Quest are not recommended for EPP testing.

Molecular Testing Laboratory:

Sema4
62 Southfield Ave
Stamford, CT 06902

Contact Information:
clientservices@sema4.com
Tel: 800-298-6470
Fax: 646-859-6870

Sema4 Molecular Testing Requisition