A novel pathogenic variant in ALAS2 gene in young Indian male with X-linked sideroblastic anemia: a case report

Congenital sideroblastic anemias are heterogenous disorders with variable phenotypic expression. The most common form is X-linked and is caused by pathogenic variants of the 5-aminolevulinate synthase 2 (ALAS2) enzyme of heme biosynthesis. A 19 year old Indian young male presented with severe microcytic anemia. Bone marrow examination revealed ring sideroblasts. Using second generation sequencing, a novel pathogenic variant (Arg204Leu) was found in exon 5 of the ALAS2 gene, establishing the diagnosis of X-linked sideroblastic anemia. On treatment with oral pyridoxine supplement the patient’s hemoglobin level returned to normal. More than 100 pathogenic variants in the ALAS2 gene have been reported to date. The Arg204Leu variant in our case adds to the XLSA pathogenic variant data base. The associated anemia is fully responsive to pyridoxine supplementation.