The portal for rare diseases and orphan drugs

Fewer than 40 cases of HEP have been described.

The disease starts in childhood. The principle clinical signs include fragile skin, bullous cutaneous lesions that are sometimes erosive, and even mutilating on the surface of the skin exposed to the sun (hands, face). Hepatoerythropioetic porphria corresponds to homozygous and composite heterozygous cases of porphyria cutanea tarda (see this term).

It is caused by a deficiency of uroporphyrinogen decarboxylase (URO-D; the fifth enzyme in the heme biosynthesis pathway) that leads to an accumulation of uroporphrin in the liver. The enzyme deficiency is a result of a mutation of the URO-D gene. At least 30 different mutations have been described, of which one substitution mutation dominates (G281D).

Diagnosis is based on evidence of an accumulation of porphyrins in urine, on their chromatographic profile, and on an elevated concentration of porphyrins in the blood. Evidence of a major deficit (<10%) of URO-D in red blood cells allows a confirmed diagnosis.

Differential diagnosis is mainly Günther disease (see this term).

Transmission is autosomal recessive. Genetic counseling should be offered to affected families to identify individuals susceptible to developing or transmitting the disease.

Management includes protecting the skin from light and, in cases of anemia, blood transfusions. Treatment with hydroxyurea and splenectomy is rarely necessary.

The long term prognosis is favorable.