Co-occurrence of Loss-of-Function GCK and ABCC8 Variants in a Pedigree With a Spectrum of Dysglycemia.

Saint-Martin, Cécile; ElSheikh, Assmaa; Jacqueminet, Sophie; Arnoux, Jean-Baptiste; Ciangura, Cécile; Bellanné-Chantelot, Christine; Shyng, Show-Ling · Diabetes · 2026

case_report · Level V

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Abstract

Genetic variants causing loss of function (LOF) of glucokinase or ATP-sensitive potassium (KATP) channels underlie diabetes or congenital hyperinsulinism, respectively, but how the co-occurrence of such variants affects glucose control is unknown. This study presents genotypes and clinical phenotypes in a pedigree with LOF variants in both GCK and the pancreatic KATP channel. Heterozygous glucokinase deletion masked infantile hyperinsulinemia and hypoglycemia caused by a heterozygous LOF KATP channel variant. Carriers of the LOF KATP variant exhibited a shift from hypoglycemia to diabetes, as has been reported previously in some carriers of KATP LOF variants.