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

Br J Haematol. 1998 Dec;103(3):839-41. doi: 10.1046/j.1365-2141.1998.01050.x.

Abstract

A R411C missense mutation of the erythroid-specific delta-aminolaevulinate synthase (ALAS2) gene was identified in a pedigree with X-linked pyridoxine-responsive sideroblastic anaemia (XLSA). The normal and the mutant cDNAs were expressed in E. coli, and the enzyme protein was purified. ALAS activity 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 accounts for low ALAS activity and a partial pyridoxine-responsiveness of the disease in the patient.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics*
  • Adolescent
  • Anemia, Sideroblastic / drug therapy
  • Anemia, Sideroblastic / enzymology
  • Anemia, Sideroblastic / genetics*
  • Humans
  • Male
  • Mutation, Missense*
  • Pedigree
  • Pyridoxine / therapeutic use

Substances

  • 5-Aminolevulinate Synthetase
  • Pyridoxine