R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity

A R411C missense mutation of the erythroid specific delta-aminolaevulinate synthase (ALAS2) gene was identified in a pedigree with X-linked pyridoxine -responsible sideroblastic anaemia (XLSA). The normal and the mutant cDNAs were expressed in E. coli, and the enzyme protein was purified. ALAS activi ty of the mutant enzyme was 12% and 25%, when incubated in the absence and the presence of pyridoxal 5'-phosphate, respectively, compared with that of the wild-type enzyme. These findings suggest that the R411C mutation accou nts for low ALAS activity and a partial pyridoxine-responsiveness of the di sease in the patient.