Intermittent hyperinsulinemic hypoglycemia due to a KCNJ11 nonsense mutation in a child with febrile status...

KCNJ11 mutations can cause congenital hyperinsulinism or diabetes mellitus. In children, seizures are typically associated with stress-induced hyperglycemia (150-200 mg/dL [8.3-11.1 mmol/L]; reference range, 73-109 mg/dL [4.1-6.1 mmol/L]). We report a 7-year-old boy with complex febrile status epilepticus who was incidentally found to have severe hypoglycemia (20 mg/dL [1.1 mmol/L]). On admission, plasma glucose was 157 mg/dL (8.7 mmol/L) after intravenous glucose administration, with an insulin level of 14.7 μU/mL (88.2 pmol/L; reference range, 2.19-9.89 μU/mL [13.1-59.3 pmol/L]) and suppressed ketones (3-hydroxybutyrate 65 μmol/L [0.065 mmol/L]; reference range, 0-74 μmol/L [0-0.074 mmol/L]). Retrospective review revealed neonatal hyperinsulinemic hypoglycemia (plasma glucose 34 mg/dL [1.9 mmol/L], insulin 5.2 μU/mL [31.2 pmol/L]). At ages 4 and 5 years, prolonged febrile seizures occurred with lower-than-expected glucose levels (103 mg/dL [5.7 mmol/L] and 127 mg/dL [7.0 mmol/L]). The mother had gestational diabetes mellitus followed by type 2 diabetes. Genetic testing identified a novel heterozygous nonsense pathogenic variant in KCNJ11 (p.Trp90Ter). A fasting study showed no hypoglycemia, and diazoxide was not initiated. KCNJ11 mutations can cause hypoglycemia beyond infancy, highlighting the need for genetic evaluation in atypical pediatric presentations.