biostudies-literatureUnknown13Koneshamoorthy ANational Health and Medical Research CouncilWe present a case of an obese 22-year-old man with activating <i>GCK</i> variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel <i>GCK</i> missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in <i>GCK</i> cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclFrontiers in endocrinology842937https://www.ebi.ac.uk/biostudies/studies/S-EPMC8969599biostudies-literatureCase Report: Hypoglycemia Due to a Novel Activating Glucokinase Variant in an Adult - a Molecular Approach.PMC8969599Seniveratne-Epa DFarrell SChin LKTaylor SSachithanandan NKoneshamoorthy ACalder GSawyer MMacIsaac RJLiu XMariana LThorn PZacharin MKrishnamurthy BTrainer AThomas HETong JKay TWHLoudovaris TLyu RMcCarthy DfalseCase Report: Hypoglycemia Due to a Novel Activating Glucokinase Variant in an Adult - a Molecular Approach.We present a case of an obese 22-year-old man with activating <i>GCK</i> variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel <i>GCK</i> missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in <i>GCK</i> cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nucl2022-01-01T00:00:00Z20222026-04-08T18:07:14.832Z2025-04-05T22:19:43.134ZS-EPMC89695993537094810.3389/fendo.2022.842937