Abstract
Congenital erythropoietic porphyria (CEP), a rare photomutilating disorder, is due to homozygosity or compound heterozygosity for mutant alleles encoding uroporphyrinogen III synthase (U3S), a cytosolic enzyme that converts hydroxymethyl bilane to uroporphyrinogen III. Deficiency of U3S results in an excess of biologically useless uroporphyrin I (URO I), which causes the photomutilation. Clinical expression of CEP is usually associated with co-existence of congenital dyserythropoietic anemia type I, also an autosomal recessive trait. We evaluated a 3-year-old boy of English-French extraction with a photosensitive bullous dermatosis; CEP was suspected. The boy had a hypochromic, microcytic anemia and thrombocytopenia from birth with hemoglobin values averaging 7.0 g/dL, MCV’s averaging 67 fL and platelet counts averaging 70,000/μL. A physical exam revealed scars on the face, hands and forearms, generalized hirsutism and splenomegaly. The diaper fluoresced under a Wood’s lamp. Fifty mL of urine contained 2,003 μg of URO (normal=trace), 92% of which was URO I. Erythrocyte U3S activity was 21% of controls, confirming the diagnosis of CEP. Red cell morphology was compatible with thalassemia and fluorescent red cells were apparent. Hb electrophoresis revealed 36.3% Hb A, 2.4% Hb A2, 59.5% Hb F and 1.8% of a fast moving peak, likely Hb Bart’s. Both parents were hematologically normal, had no evidence of porphyria, and had normal Hb electrophoreses. Genomic U3S was characterized (including the promoter), no mutations or deletions were found in the child or the parents. Characterization of the α and β-globin loci also revealed no mutations or deletions. Lack of a molecular explanation for either the low U3S activity or the β-thalassemia/thrombocytopenia phenotype led us to sequence GATA1, an X-linked transcription factor common to globin genes and the first 4 steps of the heme biosynthetic pathway in erythrocytes. A mutation was found at codon 216 in the child and on one allele of his mother, changing arginine to tryptophan (R216W). A more conservative arginine to glutamine mutation (R216Q) previously described by Yu et al. (
Author notes
Corresponding author
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal