Phosphoglycerate kinase deficiency due to a novel mutation (c. 1180A>G) manifesting as chronic hemolytic anemia in a Japanese boy

Int J Hematol. 2014 Oct;100(4):393-7. doi: 10.1007/s12185-014-1615-x. Epub 2014 Jun 17.

Abstract

Phosphoglycerate kinase (PGK) deficiency, a rare X-linked inherited disorder, manifests as various combinations of hemolytic anemia, neurological dysfunction, and myopathy. We report a Japanese boy with PGK deficiency presenting as chronic hemolytic anemia. The diagnosis of PGK1 deficiency was made at 11 months of age on the basis of low PGK enzyme activity (36.7 IU/g Hb; normal, 264-326 IU/g Hb) and the identification through PGK1 gene sequencing of a novel missense mutation: c. 1180A>G at exon 10. The mutation, which has been designated PGK-Aoto, results in a Thr394Ala amino-acid substitution at β-strand L. Because β-strand L plays an important role in the function of the hinge connecting the two domains of PGK, the Thr394Ala substitution may perturb this motion. At 3 years of age the patient has transfusion-dependent hemolytic anemia but no evidence of neuromuscular disease or developmental delay. Long-term follow-up will be needed to identify possible future clinical manifestations.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Anemia, Hemolytic* / complications
  • Anemia, Hemolytic* / enzymology
  • Anemia, Hemolytic* / genetics
  • Asian People
  • Child, Preschool
  • Chronic Disease
  • Exons*
  • Genetic Diseases, X-Linked* / complications
  • Genetic Diseases, X-Linked* / enzymology
  • Genetic Diseases, X-Linked* / genetics
  • Humans
  • Male
  • Metabolism, Inborn Errors* / complications
  • Metabolism, Inborn Errors* / enzymology
  • Metabolism, Inborn Errors* / genetics
  • Mutation, Missense*
  • Phosphoglycerate Kinase / deficiency*
  • Phosphoglycerate Kinase / genetics

Substances

  • PGK1 protein, human
  • Phosphoglycerate Kinase

Supplementary concepts

  • Phosphoglycerate Kinase 1 Deficiency