P1.007: "A Preterm Neonate with ABCC8 Mutation-Induced Congenital Hyperinsulinemia Responsive to Diazoxide Following Oral Glucose Infusion Treatment: A case report"

Introduction: Hypoglycemia is a common metabolic disorder in neonates which can be due to congenital hyperinsulinism causing unregulated insulin production. This maybe secondary to genetic mutation in genes like ABCC8 and KCNJ11. Congenital hyperinsulinism (CHI) leads to persistent refractory hypoglycemia. This can lead to seizure and brain damage therefore early diagnosis and treatment is necessary.

Case Description: We present a case of a 34-week and 5-day gestation baby, born via emergency cesarean due to being large for gestational age (LGA), with a birth weight of 5.26 kg and APGAR scores of 8/10 and 9/10. The mother had a prior abortion for fetal abnormality. The baby initially had hypoglycemia and was shifted to the Neonatal Intensive Care Unit (NICU) after repeated hypoglycemic episodes. Treatment was started with high glucose infusion rate (GIR), hydrocortisone, octreotide, and Diazoxide. A critical sample revealed hyperinsulinism. The baby was initially kept Nil per Oral (NPO) but gradually started on breast milk via NG tube, with IV GIR reduced as feeds were increased. Despite this, hypoglycemia recurred, so continuous oral GIR and hourly NG tube feeds were implemented. The baby maintained stable blood glucose and slowly with 2-hourly oral feeds, tapering and discontinuation of GIR, hydrocortisone, and octreotide could be done. Discharge was possible once the baby was stable on oral breast milk and Diazoxide. Follow-up Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18 FDG DOPA) and genetic testing revealed a uniformly enlarged pancreas and a homozygous pathogenic ABCC8 gene respectively. Stopping diazoxide at five months led to a hypoglycemic seizure, but no further episodes occurred with continued diazoxide use. The baby is under regular follow-up and has normal development milestones.

Discussion: This preterm infant with homozygous ABCC8 mutation-linked CHI atypically responded to diazoxide and oral glucose infusion, achieving glycemic stability without surgery. Despite risks of effects in brain due to hypoglycemia, normal development was maintained. The case challenges assumptions of diazoxide non-responsiveness in ABCC8 mutations and highlights oral GIR as a viable alternative in resource-limited settings, emphasizing personalized management guided by genetic insights.

Conclusion: In order to effectively treat congenital hyperinsulinism, early identification and timely administration are essential. A trial of diazoxide is warranted in congenital hyperinsulinism like in ours case wherein literature states ineffectiveness in maintaining blood sugar. Genetic testing and 18F-DOPA PET scans is warranted for decision making about medical versus surgical management. The successful switch to oral glucose infusion in this case demonstrates flexibility in handling difficulties, but more study is required to confirm its effectiveness.