A Novel Mutation Resulting in Variable Phenotypes and Pyridoxine Response in a Family with X-linked Sideroblastic Anemia.

We report a novel gene mutation c.1315A>G (p.Lys439Glu) identified in a family, which caused evidently different hematologic phenotypes. The proband was a 17-year-old man with severe microcytic hypochromic anemia, excessive ring sideroblasts in the bone marrow, and iron overload. A hemizygous mutation in exon 9, c.1315A>G (p.Lys439Glu), was identified through sequence analysis. We assume that this amino acid substitution affects the enzymatic activity of ALAS2 by affecting its interaction with the cofactor pyridoxal 5'-phosphate, since the patient was responsive to pyridoxine treatment. This novel mutation likely accounts for variable hematologic phenotypes in the family of this patient: his 15-year-old hemizygous brother was asymptomatic, while his heterozygous mother was mildly anemic.