A Novel ALAS2 Mutation Resulting in Variable Phenotypes and Pyridoxine Response in a Family with X-linked Sideroblastic Anemia

Ann Clin Lab Sci. 2017 May;47(3):319-322.


We report a novel ALAS2 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 ALAS2 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.

Keywords: ALAS2; X-Linked Sideroblastic Anemia.

Publication types

  • Case Reports

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics*
  • 5-Aminolevulinate Synthetase / metabolism
  • Adolescent
  • Anemia, Sideroblastic / drug therapy
  • Anemia, Sideroblastic / genetics*
  • Female
  • Genetic Diseases, X-Linked / drug therapy
  • Genetic Diseases, X-Linked / genetics*
  • Heterozygote
  • Humans
  • Iron Overload / genetics
  • Male
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Pyridoxal Phosphate / metabolism
  • Pyridoxine / therapeutic use*


  • Pyridoxal Phosphate
  • 5-Aminolevulinate Synthetase
  • ALAS2 protein, human
  • Pyridoxine

Supplementary concepts

  • X-linked sideroblastic anemia