The portal for rare diseases and orphan drugs

Since its description at the end of the 19th century, about 200 cases have been reported in the literature.

The disease most often manifests at birth with extreme cutaneous photosensitivity that is severe and mutilating. The principle signs include cutaneous lesions that are bullous and rapidly erosive on the surface of skin exposed to the sun and light (hands, face, feet). Urine is often very red/brown and colors the diaper of affected infants. In very severe forms, patients present with hemolysis of differing severity. Significant splenomegaly can appear, linked with hemolytic anemia. Bone involvement is constant, with rarefaction of bony architecture and a risk of multiple fractures.

Congenital erythropoietic porphyria is caused by a deficiency of uroporphyrinogen- synthase (URO-S; the fourth enzyme in the heme biosynthesis pathway) leading to a massive accumulation of isomeric I porphyrins (uro and coproporphyrins) in the bone marrow. The enzyme deficiency is caused by mutations of the UROS gene, coding for URO-S. Transmission is autosomal recessive. It should be noted that there is a certain degree of genotype-phenotype correlation by the identification of ``severe'' or ``moderate'' mutations. In 50% of cases the ``severe'' mutation C73R is present.

Diagnosis is based on the evidence of a massive accumulation of isomeric I porphyrins in the urine and blood. The evidence of a deficiency of URO-S in red blood cells and the identification of causal mutations of the UROS gene allow a confirmed diagnosis.

Differential diagnosis can include hepatoerythropioetic porphyria (see this term).

Antenatal diagnosis is possible, in families at risk, by analysis of amniotic fluid, measurement of URO-S and/or molecular genetic analysis of the amniotic cells.

Management of the disease is often difficult becausehemolytic anemia, splenic sequestration and thrombocytopenia often necessitate repeated transfusions, which in turn can lead to iron overload. Splenectomy is often indicated. Intense photoprotection is required to prevent the appearance and aggravation of cutaneous lesions. There is a constant risk of the lesions becoming infected but generally this is controlled by antibiotic therapy.

In severe forms hemolytic anemia and, in particular, thrombocytopenia dominate the prognosis and greatly diminish the life expectancy of patients. The multiple fractures often cause mobility disabilities. Bone marrow transplantation has recently spectacularly improved the prognosis of congenital erythropoietic porphyria (particularly if the patient is young) by healing cutaneous lesions and hemolytic anemia and causing them to disappear. A project exploring ex-vivo genetic treatment of bone marrow cells is currently in progress.