Albertine Donker

Chapter 3 106 DISORDERS DUE TO DEFECTS IN THE HEME AND/OR IRON-SULPHUR CLUSTER SYNTHESIS 3A. Sideroblastic anemia due to defects in SLC25A38 Pathogenesis and epidemiology SLC25A38 (OMIM 610819) encodes a protein on the inner membrane of the mitochondria of hematopoietic cells, especially erythroblasts, and is essential for the heme synthesis ( Figure 1 ). 66 Its specific function is not known, but it has been hypothesized that SLC25A38 facilitates 5-aminolevulinic acid (ALA) production by importing glycine into mitochondria or by exchanging glycine for ALA across the mitochondrial inner membrane. Defects in SLC25A38 result in severe congenital sideroblastic anemia with microcytic hypochromic erythrocytes. 66 Until now 26 patients have been reported with 20 different mutations. 66,67 The inheritance pattern is autosomal recessive; heterozygous relatives are not anemic. Clinical presentation and diagnosis Patients present with severe, often transfusion dependent, microcytic hypochromic anemia in childhood, which is clinically similar to thalassemia major. Bone marrow smears show ringed sideroblasts. Serum ferritin levels and TSAT are increased, even before treatment with erythrocyte transfusions. Treatment Symptomatic treatment consists of erythrocyte transfusions and iron chelation. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment and was performed in eight out of 29 patients and resulted in disease free survival in four patients (follow up < 5 years). 3 B. X-linked sideroblastic anemia with ataxia due to defects in ABCB7 Pathogenesis and epidemiology ABCB7 (OMIM 300135) on the X-chromosome encodes a protein in the inner membrane of the mitochondria, which is the putative mitochondrial exporter of Fe-S