Clinical characterization and hematopoietic stem cell transplant outcomes for congenital sideroblastic anemia caused by a novel pathogenic variant in SLC25A38

Background Congenital sideroblastic anemia (CSA) constitutes an uncommon category of inherited anemia often associated with pathologic iron accumulation. Pathogenic variants in several genes have been identified as causative for CSA. Autosomal recessive pathogenic variants in the mitochondrial glycine transporter SLC25A38 have been implicated in a subset of patients with CSA. Procedure We describe seven individuals of Canadian Cree descent with a known or inferred homozygous novel founder missense variant in SLC25A38 (c.560G>A, p.Arg187Gln). Results All individuals presented as young children (median age 6 months) with severe microcytic, hypochromic anemia associated with pretransfusion iron overload, requiring red cell transfusion support and iron chelation. Six individuals received pyridoxine supplementation; two demonstrating transient partial responses. Three individuals underwent allogeneic hematopoietic stem cell transplantation (HSCT). One individual with significant iron loading died in the posttransplant period due to complications of sepsis. The other two individuals remain transfusion‐free following HSCT. Conclusions Despite a common genetic etiology, phenotypic variability was noted in this cohort. A transient response to pyridoxine was noted in two individuals but should not be considered a long‐term therapeutic strategy. HSCT was curative when performed before significant iron loading occurred. Early identification of CSA and timely HSCT can result in excellent long‐term outcomes.