Department of Clinical Medicine, Tohoku University School of Medicine, Sandai, Japan.
A novel missense mutation, G663A, in exon 5 of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) was identified in a Japanese male with pyridoxine-responsive sideroblastic anemia. Activity of the mutant delta-aminolevulinate synthase protein expressed in vitro was 15.1% compared with the normal control, but was increased up to 34.5% by the addition of pyridoxal 5'-phosphate, consistent with the clinical response of the patient to pyridoxine treatment. The same mutation was also detected in genomic DNa from the oral mucosal membrane of the patiet; however, it was not detected in other family member. These findings suggest that this G663A mutation is responsible for sideroblastic anemia in the proband, and may be an index mutation in this pedigree.