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

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.

• Authors: Attia Kalim, Patricia Fitzsimons, Claudia Till, Malkanthi Fernando, Philip Mayne, Jorn Oliver Sass, Ellen Crushell
• Journal: Brain & development (Brain Dev) Vol. 39 Issue 6 Pg. 536-538 (Jun 2017) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 28190537 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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