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Genetic Testing Lab

Test Catalog Molecular Genetics Laboratory Erythropoietic Protoporphyria

Erythropoietic Protoporphyria

Test Description:

EPP and XLP are both protoporphyrias with similar symptoms and similar biochemical findings, but each is caused by mutations in a different gene. EPP is a deficiency of the enzyme, ferrochelatase in the heme biosynthesis pathway, due to mutations in FECH gene. The inheritance of EPP follows an autosomal recessive pattern: most cases due to a severe mutation on one FECH allele (inherited from one parent), and a specific common genetic variation on the other FECH allele (inherited from the other parent). This common genetic variation causes reduced production of the enzyme, but does not cause disease in the absence of a severe mutation. Alternatively, some EPP cases result from two severe FECH gene mutations, one inherited from each parent. Biochemical testing, specifically total and fractionated erythrocyte protoporphyrin assay, can often be done between XLP and EPP. 

Symptoms usually first occur in early childhood and include sun sensitivity, marked by severe pain and swelling of sun-exposed areas, but typically with no blistering or scarring. Both EPP and XLP result in significant elevations of protoporphyrins in the liver, sometimes resulting in severe liver complications that are difficult to treat and sometimes require liver transplantation. 

Molecular analysis for XLP is performed in this laboratory as part of the "Erythropoietic Protoporphyria Panel" (analysis of the FECH gene for EPP and ALAS2 exon 11 for XLP). DNA analysis of the FECH gene is performed by full gene sequencing of all exons (coding regions), 20-30 base pairs into the introns (including splice sites), and the promoter region. This methodology should identify >98% of mutations listed in the Human Gene Mutation Database as well as novel mutations. 

Targeted mutation analysis, looking for the specific family's FECH mutation or the specific common variant, can also be performed. Documentation of the family's mutation must be provided. 

Prenatal diagnosis is also available. Prior to ordering prenatal testing, please contact our laboratory at 212-241-7518 to discuss. 

Specimen Requirements: 

Post-natal

  • Full DNA analysis ("Erythropoietic Protoporphyria Panel" only): 20ml of whole blood in EDTA (anticoagulant) tubes (lavender top) OR extracted DNA (50μl with concentration of 200ng/μl). 
  • Targeted Mutation Analysis: 20ml of whole blood in EDTA (anticoagulant) tubes (lavender top) OR extracted DNA (30μl with concentration of 200ng/μl) OR buccal cells (buccal brushes MUST be requested from the laboratory). 

Prenatal: Testing requires prior documentation of parental mutation.

  • Chorionic Villi: 5-10 mg in conical tube with sterile saline OR transport media
  • Amniotic Fluid: 10 ml in conical tube
  • Cultured Cells: two confluent T-25 flasks

     Additionally, please send: 

  • 5-10 ml maternal blood in EDTA (lavender top) required to perform MCC studies on all prenatal samples and in case maternal confirmation studies are necessary
  • 5-10 ml paternal blood in EDTA (lavender top) in case paternal confirmation studies are necessary

Shipping: Ship at room temperature.

Turnaround Time:

Post-natal: 10-14 days

Prenatal: 3-5 days

CPT Codes: 

Full gene sequencing: 81406, 81479, G0452

Targeted mutation analysis for family mutation(s): 81404, 81479, G0452

Targeted mutation analysis for the specific common variant: 81403, 81479, G0452

Consent Form: Porphyria Genetic Testing Consent [PDF]

Requisition Form: Porphyria Testing Requisition [PDF]