Congenital Erythropoietic Porphyria


Related Gene(s): UROS

Congenital erythopoietic porphyria (CEP), also known as Gunther disease, is caused by a deficiency of the enzyme uroporphyrinogen III synthase (URO-synthase) in the heme biosynthesis pathway due to mutations in the UROS gene. The disorder is autosomal recessive. CEP is one of the most severe porphyrias. Symptoms usually begin soon after birth or in early childhood. Some severe cases have been diagnosed before birth as a cause of anemia and fluid accumulation in the fetus (fetal hydrops). Less severe cases may occur in adults in association with another bone marrow condition.

Skin photosensitivity results in severe blistering and scarring, often with mutilation and loss of facial features and fingers. Increased hair growth (hypertrichosis) on sun-exposed skin, brownish-colored teeth (erythrodontia), and reddish-colored urine are common. There may be bone fragility due to expansion of the bone marrow and vitamin deficiencies, especially vitamin D. Red blood cells have a shortened life span, and mild or severe hemolytic anemia often results. Synthesis of heme and hemoglobin is actually increased to compensate for the shortened red blood cell survival and is associated with splenomegaly. Bacteria may infect the damaged skin and contribute to mutilation and scarring.

DNA analysis of the UROS 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 >97% of gene mutations reported in the Human Gene Mutation Database, as well as novel mutations. Molecular analysis of ALAS2 exon 11 (for XLP) is performed in conjunction with full sequencing of the UROS gene.

Targeted mutation analysis can be performed for family members of individuals whose UROS gene mutations have been identified previously. Documentation of the family’s mutations must be provided. Prenatal diagnosis is also available. Prior to ordering prenatal testing, please contact our laboratory at 212-241-7518.


Specimen Requirements

Prenatal

  • Testing requires prior documentation of parental mutations.
  • 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: 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.