Albertine Donker

Rare Inherited Iron and Heme-related Anemias 105 3 Treatment The seven described patients with severe anemia were treated with erythrocyte transfusions. Three patients received oral iron, which increased Hb and led to transfusion independency in one patient. Three patients received EPO, resulting in an increase of Hb, but - based on the clinical course of one patient - not in prevention of liver iron loading. 62 Erythrocyte transfusions and probably also oral or intravenous iron cause additional liver iron loading. Chelation was not effective in reducing liver iron and resulted in decrease of Hb (unpublished data, Tchernia and Beaumont 1,62 ). 2C. Sideroblastic anemia due to defects in STEAP3 Pathogenesis and epidemiology STEAP3 (OMIM 609671) encodes a ferroreductase, responsible for the reduction of Fe 3+ to Fe 2+ in endosomes of erythroblasts ( Figure 1 ). 63 Mice studies show that absence or reduced activity of ferroreductase results in severe microcytic anemia, which can be corrected by introduction of a functional STEAP3 . 64 The first and so far only human STEAP3 mutation was recently described in three siblings born to healthy, non-consanguineous parents. 65 Clinical presentation and diagnosis The three siblings displayed a transfusion-dependent severe hypochromic anemia with a normal to slightly decreased MCV. Serum iron and ferritin were normal to increased, while TSAT was markedly increased. A bone marrow smear in the index patient showed ring sideroblasts. Liver biopsy after multiple erythrocyte transfusions showed iron loading. All patients suffered from gonadal dysfunction, as described for STEAP3 deficient mice. 65 A heterozygous nonsense STEAP3 mutation was inherited from the father, while no defect was found in the mother. The authors explain the normal phenotype of the father by the STEAP3 expression of the ‘healthy’ allele in lymphocytes, which was significantly higher than in his affected children. Treatment Treatment consisted of a combination of erythrocyte transfusions and chelation while EPO increased the transfusion interval.