Erythropoietic Protoporphyria


Related Gene(s): FECH, ALAS2

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are both protoporphyrias with similar symptoms and similar biochemical findings, but each is caused by mutations in a different gene. EPP is caused by a deficiency of the enzyme, ferrochelatase in the heme biosynthesis pathway, due to mutations in the FECH gene. The inheritance of EPP follows an autosomal recessive pattern. In most cases, this is 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 mutations, one inherited from each parent. Biochemical testing, specifically assays of free- and zinc-complexed erythrocyte protoporphyrin, can help to distinguish between XLP and EPP.

Symptoms usually first occur in early childhood and include phototoxicity, causing severe pain and swelling of sun-exposed areas, but typically without blistering or scarring. Both EPP and XLP can result in significant elevations of protoporphyrins in the liver, causing severe liver complications in about 5% of cases that 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 >95% 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

Prenatal

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

Postnatal

  • For adults
  • Full DNA sequence analysis (“Erythropoietic Protoporphyria Panel” only): 10-20 mL of whole blood in EDTA (anticoagulant) tubes (lavender top) or extracted DNA (50 µL with concentration of 200 ng/µL)
  • Targeting mutation analysis: 20 mL of whole blood in EDTA (anticoagulant) tubes (lavender top) or extracted DNA (30 µL with concentration of 200 ng/µL) or buccal cells (buccal brushes must be requested from laboratory)

  • For newborns or children
  • Blood: 2 mL in pediatric EDTA tube (lavender top) or 2 mL in pediatric ACD tube (yellow top) from patient

Ordering Information

Shipping

  • Ship at room temperature

Turnaround Time

  • Prenatal: 3-5 days
  • Postnatal: 10-14 days


Resources

Consent and requisition forms available soon. For additional assistance, please contact us.