CONGENITAL ERYTHROPOIETIC PORPHYRIA SUCCESSFULLY TREATED BY ALLOGENEIC BONE-MARROW TRANSPLANTATION

The long-term biochemical and clinical effectiveness of allogenic bone marrow transplantation (BMT) was shown in a severely affected, transf usion-dependent 18-month-old female with congenital erythropoietic por phyria (CEP), an autosomal recessive inborn error of heme biosynthesis resulting from mutations in the uroporphyrinogen III synthase (URO-sy nthase) gene. Three years post-BMT, the recipient had normal hemoglobi n, markedly reduced urinary porphyrin excretion, and no cutaneous lesi ons with unlimited exposure to sunlight. The patient was homoallelic f or a never URO-synthase missense mutation, G188R. that expressed less than 5% of mean normal activity in Escherichia coli, consistent with h er transfusion dependency. Because the clinical severity of CEP is hig hly variable, ranging from nonimmune hydrops fetalis to milder, later onset forms with only cutaneous lesions, the importance of genotyping newly diagnosed infants to Select severely affected patients for BMT i s emphasized. In addition, the long-term effectiveness of BMT in this patient provides the rationale for future hematopoietic stem cell gene therapy in severely affected patients with CEP. (C) 1998 by The Ameri can Society of Hematology.