KCNJ11

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in children, most frequently caused by pathogenic variants in ABCC8 or KCNJ11, encoding subunits of the pancreatic KATP channel (1,3). Case presentation: A previously healthy 7-year-old boy presented with recurrent early morning hypoglycaemia associated with lethargy, sweating and confusion. Biochemical evaluation confirmed hyperinsulinaemic hypoglycaemia with suppressed ketones and free fatty acids. He responded completely to diazoxide, indicating functional KATP channel involvement. Whole-exome sequencing identified no clearly pathogenic variants but several variants of uncertain significance (VUS) in ABCC8, KCNJ11, and HNF1A, including a homozygous deep intronic variant (ABCC8: c.2256-50T>C) potentially affecting splicing (2,3). Outcome: The patient achieved full remission with diazoxide therapy, frequent carbohydrate intake, and bedtime cornstarch supplementation. Conclusion: This case illustrates the diagnostic complexity of CHI with multiple VUS and highlights the clinical utility of diazoxide responsiveness as a functional marker of KATP channel dysfunction. Functional studies of deep intronic variants and polygenic interactions remain essential for accurate molecular diagnosis (2,3).