title: 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.affiliation: National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland.
authors.forename: Attia
authors.initials: A
authors.lastname: Kalim
authors.affiliation: Department of Clinical Biochemistry, Temple Street Children University Hospital, Dublin, Ireland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitzsimons
authors.affiliation: Department of Natural Sciences, Bonn-Rhein-Sieg-University of Applied Sciences, Rheinbach, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Till
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Malkanthi
authors.initials: M
authors.lastname: Fernando
authors.affiliation: Department of Clinical Biochemistry, Temple Street Children University Hospital, Dublin, Ireland.
authors.forename: Philip
authors.initials: P
authors.lastname: Mayne
authors.affiliation: Department of Natural Sciences, Bonn-Rhein-Sieg-University of Applied Sciences, Rheinbach, Germany.
authors.forename: Jorn Oliver
authors.initials: JO
authors.lastname: Sass
authors.affiliation: National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland. Electronic address: ellen.crushell@cuh.ie.
authors.forename: Ellen
authors.initials: E
authors.lastname: Crushell
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000000981:diagnostic imaging / Q000235:genetics; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D010770:Phosphotransferases / Q000172:deficiency / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*
chemical_list: D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020670:glycerate kinase
keywords: Autism; Enantioselective gas chromatography; Fructose; Glycerate; Glyceric aciduria; Serine; Urine organic acid analysis