AbstractCongenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 × 109/L (70 000/μL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with β-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F, and 1.8% of an unidentified peak. No UROS or α- and β-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia.
Congenital erythropoietic porphyria: Insight into the molecular basis of the disease