DNA Testing for Porphyria


The Mount Sinai Genetic Testing Laboratory in New York City is proud to announce availability of DNA testing for seven Porphyrias, including Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), familial Porphyria Cutanea Tarda (f-PCT), Hepatoerythropoietic Porphyria (HEP), Erythropoietic Protoporphyria (EPP) and Congenital Erythropoietic Porphyria (CEP). This is the only laboratory in the United States that offers DNA testing for all of these Porphyrias. The testing program was developed with a grant from the American Porphyria Foundation. We thank the Porphyria patients who sent us their blood to develop and validate these tests.

Before requesting DNA testing, it is recommended that patients have biochemical testing (urinary, stool and/or plasma porphyrins and porphyrin precursors (porphobilinogen (PBG) and aminolevulinic acid (ALA)) 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 and requires only a small amount of blood sent to the laboratory at room temperature. 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.

It is important for patients to realize the limitations of DNA testing. Each Porphyria is caused by a mutation in the DNA sequence of a specific gene. Thus, the diagnosis of a specific Porphyria determines what gene to test. Diagnosis of the specific Porphyria can be difficult because the three acute Hepatic Porphyrias (AIP, HCP, VP) typically have similar acute symptoms, biochemical findings, and responses to treatment. This means, for example, that if a patient has been given the diagnosis of AIP and no AIP gene mutation is identified, it is possible that the patient has a different acute Porphyria. For patients with symptoms of an acute Porphyria, but without a specific diagnosis, we offer a "triple test," which includes DNA testing for the three major acute hepatic Porphyrias (AIP, HCP, and VP).

DNA testing involves sophisticated DNA sequencing which is multi-procedural, labor intensive, and expensive. In the Porphyrias, there are no common mutations so the entire gene must be sequenced in each new family.