Diazoxide-Responsive Congenital Hyperinsulinism in a Preterm Infant With Homozygous ABCC8 Mutation: A Case Report

Congenital hyperinsulinism (CHI) is characterized by inappropriate insulin secretion resulting in persistent neonatal hypoglycemia. CHI is often linked to mutations in the ABCC8 and KCNJ11 genes and can lead to persistent hypoglycemia, seizures, and neurological injury, making early diagnosis and management essential.

We describe a late-preterm Nepalese infant born at 34 weeks and 5 days of gestation, weighing 5.26 kg, to a 32-year-old gravida four nondiabetic mother. The infant developed significant hypoglycemia just 2 h after birth. Despite a glucose infusion rate (GIR) of 12 mg/kg/min, the infant had persistent hypoglycemia. A critical sample confirmed hyperinsulinism, prompting treatment with octreotide, intravenous (IV) GIR of 17 mg/kg/min and later diazoxide. Due to limited IV access, a continuous enteral GIR of 9 mg/kg/min was administered through an orogastric (OG) tube. Genetic testing revealed a homozygous pathogenic p.Arg1214Gln mutation in the ABCC8 gene, and ¹⁸F-DOPA PET-CT (2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission computed tomography) showed diffuse pancreatic uptake. At 5 months, interruption of diazoxide therapy led to a hypoglycemic seizure (blood glucose level: 29 mg/dL), which resolved after the treatment resumed. Despite the typical association of homozygous ABCC8 mutations with diazoxide nonresponsiveness, this infant achieved sustained glycemic control on diazoxide. On subsequent follow-ups, the child remains stable and continues to achieve normal developmental milestones.

Early recognition and timely management are crucial in effective management of CHI. This case shows rare diazoxide responsiveness in homozygous ABCC8 mutation. This case suggests that a carefully monitored therapeutic trial of diazoxide may still be reasonable in selected patients with homozygous ABCC8 mutations before concluding complete medical unresponsiveness.