Treatment of congenital erythropoietic porphyria in children by allogeneic stem cell transplantation: a case report and review of the literature

Abstract

Summary:Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder of porphyrin metabolism in which the genetic defect is the deficiency of uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity and mutilating skin lesions. We describe the case of a 23-month-old boy who was cured of his CEP by a matched-sibling allogeneic bone marrow transplant, and review the published clinical experience regarding transplantation in this disease. He is alive and disease-free 15 months post transplant. All of his disease manifestations except for the erythrodontia have resolved. His UIIIC level and stool and erythrocyte porphyrin metabolites have almost completely corrected. He is the sixth child reported to be cured of this disease by stem cell transplantation, five cases being long-term survivors. If patients with this disease have an HLA-matched sibling, then stem cell transplantation should be strongly considered because this is currently the only known curative therapy. Bone Marrow Transplantation (2001) 27, 101-105. Keywords: congenital erythropoietic porphyria; porphyria; stem cell transplantation; bone marrow transplantation Congenital erythropietic porphyria (CEP), or Gunther's disease, is one of the rarest of the porphyrias, a group of metabolic disorders in which excessive quantities of porphyrins or their precursors are produced. This autosomal recessive disorder is caused by a defect of the enzyme uroporphyrinogen III cosynthase (UIIIC) that leads to an accumulation of uroporphyrinogen I and coproporphyrinogen I in all tissues. The primary clinical manifestations of this accumulation include erythrodontia, bone fragility, hypertrichosis,

Congenital Erythropoietic Porphyria: Characterization of Murine Models of the Severe Common (C73R/C73R) and Later-Onset Genotypes

“…This human inborn error of heme biosynthesis is primarily an erythroid disease, since successful bone marrow or hematopoietic stem cell transplantation is curative (18) and since a hepatic-specific UROS deficiency did not compromise hemoprotein function (21). Because of the rarity of the disease, the extremely variable phenotypic expression and the limits of human experimentation, few hematologic studies of severe and later-onset CEP patients were reported.…”

“…Additional manifestations often include hypertrichosis, alopecia and erythrodontia. Successful bone marrow or hematopoietic stem cell transplantation is essentially curative but is associated with increased morbidity and mortality (16)(17)(18)(19).…”

Pediatric photosensitivity

“…It manifests in the first year of life with severe photosensitivity, which causes bullae formation and mutilating scarring, in addition to erythrodontia, bone fragility, hemolytic anemia, ocular involvement, and hypertrichosis. Stem cell transplantation has been reported as a curative therapy (28). Importantly, prompt diagnosis should be made if possible in these newborns, with absolute contraindication of phototherapy for treatment of neonatal jaundice to avoid a widespread acute phototoxic bullous reaction (26).…”

Two Brothers With Mild Congenital Erythropoietic Porphyria Due to a Novel Genotype

“…Other treatment modalities with limited efficacy include oral beta carotene, intravenous hematin, plasmapheresis, hydroxychloroquine, oral charcoal, and other porphyrin binders. 2,17 For severely affected patients who are transfusion dependent, erythrocyte transfusion, 18 hydroxyurea, 19 and splenectomy 20 appear effective, at least until adolescence; stem cell or bone marrow transplantation has been curative. 20,21 In vitro gene transfer studies have demonstrated restoration of URO-synthase activity, suggesting the future potential effectiveness of gene therapy.…”

“…2,17 For severely affected patients who are transfusion dependent, erythrocyte transfusion, 18 hydroxyurea, 19 and splenectomy 20 appear effective, at least until adolescence; stem cell or bone marrow transplantation has been curative. 20,21 In vitro gene transfer studies have demonstrated restoration of URO-synthase activity, suggesting the future potential effectiveness of gene therapy. [22][23][24] In summary, we describe 2 brothers with CEP who have an unusually mild phenotype due to a novel heterozygous genotype that consists of a promoter mutation (−76G→A) and an exonic missense mutation (G225S).…”