X-Linked Protoporphyria


Related Gene(s): 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. XLP is sometimes called a “variant form of EPP.” XLP is an X-linked disorder caused by a mutation in exon 11 of the ALAS2 gene, resulting in the increased production of the erythroid-specific enzyme aminolevulinic acid-synthase 2 in the heme biosynthesis pathway. 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 exon 11 of the ALAS2 gene is performed by full gene sequencing of the exon (coding region) and 20-30 base pairs into the intron (including the splice site). The detection rate for exonic mutations is >99%.

After the index case in a family is identified (or confirmed if initially identified elsewhere), targeted mutation analysis, can also be performed to look for the specific family’s ALAS2 exon 11.

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)
  • Targeted 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.