Classification of GCK-MODY in a child with mild hyperglycemia and islet autoantibody positivity: a diagnostic...

We report a 9-year-old female who presented with mild, persistent hyperglycemia, with hemoglobin A1c and oral glucose tolerance test results in the prediabetes range, relatively preserved C-peptide, and mildly positive glutamate decarboxylase 65 autoantibody levels. A strong family history of lean, noninsulin-dependent diabetes suggested a possible monogenic cause. Genetic testing with a 28-gene maturity-onset diabetes of the young (MODY) panel identified a heterozygous variant of uncertain significance in GCK (NM_000162.5:c.179C>T [p.Thr60Ile]). Following review by the ClinGen Monogenic Diabetes Variant Curation Expert Panel, the GCK variant was reclassified as pathogenic, confirming a diagnosis of glucokinase (GCK)-MODY/GCK-hyperglycemia, a stable form of mild hyperglycemia that does not require pharmacologic treatment. Subsequent genetic testing of the father confirmed paternal inheritance. Due to the presence of a positive islet autoantibody, she was counseled on the potential for autoimmune diabetes and advised to continue periodic monitoring. This case illustrates the diagnostic complexity of differentiating monogenic hyperglycemia from autoimmune diabetes in children.