Further evidence that d-glycerate kinase (GK) deficiency is a benign disorder

Brain Dev. 2017 Jun;39(6):536-538. doi: 10.1016/j.braindev.2017.01.005. Epub 2017 Feb 9.

Abstract

d-Glyceric aciduria is caused by deficiency in d-glycerate kinase (GK) due to recessive mutations in the GLYCTK gene. GK catalyzes the conversion of d-glycerate to 2-phosphoglycerate which is an intermediary reaction in the catabolism of serine and fructose. Deficiency of GK leads to accumulation of d-glycerate, which may be detected in urine organic acid analysis. Debate exists as to whether this is a benign or disease-causing disorder as the reported phenotypes vary significantly. We report two siblings from a consanguineous Pakistani family. The index case is a 5year old boy with severe autism and global developmental delay. His urine organic acid analysis showed markedly increased excretion of glycerate, determined as d-form by enantioselective gas chromatography. There was no oxalic aciduria. His younger sister (3years old) is asymptomatic and developmentally normal (already bilingual). Her urine showed similar amounts of d-glycerate. Both children are homozygous for the novel mutation c.767C>G in exon 5 of the GLYCTK gene, predicted to affect the enzyme by replacing the evolutionarily conserved Proline with Arginine (P256R). Both parents are heterozygous carriers. These cases support the view that d-glycerate kinase deficiency is a benign disorder. Long term follow-up studies with a greater number of individuals may be required for further confirmation.

Keywords: Autism; Enantioselective gas chromatography; Fructose; Glycerate; Glyceric aciduria; Serine; Urine organic acid analysis.

Publication types

  • Case Reports

MeSH terms

  • Carbohydrate Metabolism, Inborn Errors / diagnostic imaging
  • Carbohydrate Metabolism, Inborn Errors / genetics
  • Child, Preschool
  • Family Health
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases / deficiency
  • Phosphotransferases / genetics

Substances

  • Phosphotransferases
  • Phosphotransferases (Alcohol Group Acceptor)
  • glycerate kinase

Supplementary concepts

  • D-glycericacidemia