DNA testing for Porphyria

Rose Window — DNA cross-sectionThe 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 Erythropoietc 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 (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 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 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 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.

The cost for DNA testing for one specific porphyria is $802 to $922, depending on the specific porphyria being tested. Once a mutation is identified, the cost for DNA testing of other family members is $226 per person. For patients with symptoms of an acute porphyria, but whose specific porphyria has not been identified, the “Acute Porphyrias Panel” for analysis of the genes causing the three acute porphyrias can be performed for $1882, a savings of $700 over sequencing each gene separately. Results from DNA testing are typically available in 2 to 4 weeks.

The Mount Sinai Genetic Testing Laboratory, Porphyria DNA Testing Laboratory accepts some insurance; please contact the genetic counselor at the laboratory for current information. Alternatively, payment can be made by credit card or check, which must accompany the patient's blood sample. A receipt will be provided, but depending on the patient's insurance company and policy, the reimbursement will vary and some companies will not pay for Porphyria testing at all. By New York State regulation, DNA testing for any genetic disorder must be ordered by a physician who also must sign the requisition form and who will receive the results. A patient must also read and sign a consent form which explains DNA testing and offers counseling.

Please contact the genetic counselor, Dana Doheny, MS, CGC, by email (porphyria@mssm.edu or dana.doheny@mssm.edu) or telephone (212-659-6779, direct-line; 866-322-7963, toll-free) for the required forms (including sample requirements, shipping instructions, test requisition, and consent form), to arrange for testing, and/or for additional information.

 

The Mount Sinai Genetic Testing Laboratory, Porphyria DNA Testing Laboratory, Department of Genetics & Genomic Sciences, The Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14-74, Box 1498, New York City, NY 10029-6574.