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Hepatoerythropoietic porphyria
A rare form of hepatic porphyria characterized by bullous photodermatosis.
ORPHA:95159
Fewer than a hundred cases of hepato-erythropoietic porphyria (HEP) have been described worldwide.
The disease begins in childhood. The main clinical signs include skin fragility, and sometimes erosive or even mutilating bullous skin lesions on sun-exposed surfaces (hands, face). Anemia and splenomegaly may be present. At bone level, delayed metacarpophalangeal growth is usually present. Hepatoerythropoietic porphyria corresponds to homozygous or heterozygous compound cases of porphyria cutanea tarda.
The disease is due to a deficiency of uroporphyrinogen decarboxylase (UROD; the fifth enzyme in the heme biosynthesis pathway) resulting from a mutation in the UROD gene (NM_000374.5), which leads to an accumulation of porphyrins mostly in the liver. At least 30 different mutations have been described in the UROD gene, including one predominant substitution: G281D.
Diagnosis is based on evidence of porphyrin accumulation in urine and stool with a characteristic chromatographic profile, and very high porphyrin concentrations in plasma and erythrocytes. The presence of a major (< 10%) UROD deficiency in red blood cells confirms the diagnosis. Skin biopsy is not very informative and is not recommended.
Günther's disease is the main differential diagnosis.
Antenatal diagnosis is theoretically possible, but is not proposed.
Transmission pattern is autosomal recessive. Genetic counseling should be offered to affected families to identify individuals likely to develop or transmit the disease. Genetic counselling should be offered to at-risk couples (both individuals are carriers of a heterozygous pathogenic variant) informing them that there is a 25 % risk of having an affected child at each pregnancy.
Care and support mainly involves protecting the skin against light, and blood transfusions in case of anemia. Treatment with hydroxyurea and splenectomy are rarely necessary. Chloroquine and phlebotomy are of limited effectiveness in the treatment of hepato-erythropoietic porphyria.
The long-term prognosis is good.
Last update: March 2024 - Expert reviewer(s): Dr Neila TALBI | MetabERN*
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