Congenital erythropoietic porphyria

Author: Dr Chin-Yun Lin, Dermatology Registrar, Auckland Hospital, New Zealand, 2010.


What is congenital erythropoietic porphyria?

Congenital erythropoietic porphyria (CEP) is very rare metabolic disorder affecting the synthesis of haem, the iron-containing pigment that binds oxygen onto red blood cells.

It was initially described by Hans Gunther so is also known as Gunther disease.

What is the cause of congenital erythropoietic porphyria?

CEP is an inherited disorder in which there is a mutation in a gene on chromosome 10 that encodes uroporphyrinogen III synthase. CEP is autosomal recessive, which means an abnormal gene has been inherited from both parents. Carriers of a single abnormal gene do not usually exhibit any signs or symptoms of the disorder.

Homozygous mutation leads to deficiency of uroporphyrinogen III synthase and uroporphyrinogen cosynthetase.

Normally, activity of the enzyme uroporphyrinogen III synthase leads to the production of isomer III porphyrinogen, needed to form haem.

When uroporphyrinogen III synthase is deficient, less isomer III and more isomer I porphyrinogen is produced. Isomer I porphyrinogens are spontaneously oxidized to isomer 1 porphyrins, which accumulate in the skin and other tissues. They have a reddish hue.

Porphyrins are photosensitisers, ie, they injure the tissues when exposed to light.

Clinical features of congenital erythropoietic porphyria

Clinical manifestations of CEP may be present from birth and can range from mild to severe.

  • Photosensitivity results in blisters, erosions, swelling and scarring of skin exposed to light.
  • Hair growth in light-exposed areas may be excessive (hypertrichosis).
  • Teeth may be red/brown in colour and fluoresce when exposed to UVA (Wood light).
  • Eyes may be inflamed and develop corneal rupture and scarring.
  • Urine may be reddish pink.
  • Breakdown of red blood cells leads to haemolytic anemia.
  • Severe haemolytic anaemia results in an enlarged spleen and fragile bones.
  • Chronic damage to skin, cartilage, and bones can cause mutilation and deformities.

What investigations should be done?

The diagnosis of CEP is confirmed by finding high levels of porphyrins in urine, faeces and circulating red blood cells. Findings are:

  • Raised urinary uroporphyrin I and coproporphyrin I
  • Raised faecal coproporphyrin I
  • Stable fluorescence of circulating red blood cells on exposure to UVA.

What is the treatment for congenital erythropoietic porphyria?

CEP persists lifelong.

It is essential to protect the skin from all forms of daylight to reduce pain, burning, swelling and itching. Indoors, incandescent lamps are more suitable than fluorescent lamps and protective films can be placed on the windows to reduce the light that provokes porphyria.

  • Many sunscreens are not effective, because porphyrins react with visible light. Those containing zinc and titanium or mineral makeup may provide partial protection.
  • Sun protective clothing is more effective, including densely woven long-sleeve shirts, long trousers, broad-brimmed hats, bandanas and gloves.
  • Supplemental Vitamin D tablets should be taken.

Some patients have been helped by:

  • High dose beta carotene, to absorb light energy;
  • Low-dose chloroquine, to increase excretion of porphyrins;
  • Blood transfusion to suppress heme production.

Bone marrow transplant has been successful in a few cases, although long term results are not yet available. At present, this treatment is experimental.

 

Related Information

References

  • James WD, Berger TG, et al. Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier 2006; 526.
  • Deybach JC, De Verneuil H, Boulechfar S, Grandchamp B, Nordmann Y. Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease). Blood 1990;75(9):1763–5.
  • Robert-Richard E, Moreau-Gaudry F, Lalanne M, et al. Effective gene therapy of mice with congenital erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells. Am. J. Hum. Genet. 2008;82(1):113–24.
  • Desnick RJ, Astrin KH. Congenital erythropoietic porphyria: advances in pathogenesis and treatment. Br J Haematol 2002;117:779-795.
  • Martin A Crook. Clinical chemistry and Metabolic Medicine, 7th edition 2006. Hodder Arnold.
  • Faraci M, Morreale G, Boeri E, et al.. Unrelated HSCT in an adolescent affected by congenital erythropoietic porphyria. Pediatr Transplant 2008;12(1):117–20.
  • Thadani H, Deacon A, Peters T. Diagnosis and management of porphyria. BMJ 2000; 320(7250):1647–51.

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