Submitted June 1, 2006
Accepted October 31, 2006
Congenital erythropoietic porphyria due to a mutation in GATA-1: the first trans-acting mutation causative for a human porphyria
John D Phillips*, David P Steensma, Michael A Pulsipher, Gerald J Spangrude, and James P Kushner
Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT
* Corresponding author; email: john.phillips{at}hsc.utah.edu.
Congenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess of 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 70,000/uL. Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with 
-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F and 1.8% of an unidentified peak. No UROS or 
and -globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA-1, 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.
