Rabbit Anti-Human GLYCTK (a.a. 251-350) Polyclonal antibody

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 5 year 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 (3 years 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. (C) 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

D-glycerate 2 kinase (DGK) is an enzyme that mediates the conversion of D-glycerate, an intermediate metabolite of serine and fructose metabolism, to 2-phosphoglycerate. Deficiency of DGK leads to accumulation of D-glycerate in various tissues and its massive excretion in urine. D-glyceric aciduria (DGA) is an autosomal recessive metabolic disorder caused by mutations in the GLYCTK gene. The clinical spectrum of DGA is highly variable, ranging from severe progressive infantile encephalopathy to a practically asymptomatic condition. We describe a male patient from a consanguineous Arab family with infantile onset of DGA, characterized by profound psychomotor retardation, progressive microcephaly, intractable seizures, cortical blindness and deafness. Consecutive brain MR imaging showed an evolving brain atrophy, thinning of the corpus callosum and diffuse abnormal white matter signals. Whole exome sequencing identified the homozygous missense variant in the GLYCTK gene [c.455T>C, NM_145262.3], which affected a highly conserved leucine residue located at a domain of yet unknown function of the enzyme [p.Leu152Pro, NP_660305]. In silico analysis of the variant supported its pathogenicity. A review of the 15 previously reported patients, together with the current one, confirms a clear association between DGA and severe neurological impairment. Yet, future studies of additional patients with DGA are required to better understand the clinical phenotype and pathogenesis.