SUN-208 Congenital Hyperinsulinism in an ABCC8 Heterozygous Carrier: A Diagnostic and Therapeutic Challenge

Abstract Disclosure: R. Navardauskaite: None. D. Denaite: None. M. Sukys: None. R. Traberg: None. P. Jarusevicius: None. Introduction: Congenital hyperinsulinism (CHI) is a rare, yet severe cause of persistent hypoglycemia in neonates and infants, driven by dysregulated insulin secretion from pancreatic β-cells. Frequently associated with mutations in ABCC8 and KCNJ11, CHI poses significant neurological risks due to recurrent hypoglycemia, which may result in developmental delays, seizures, or brain injury. The disorder may manifest in focal or diffuse forms, necessitating genetic testing and advanced imaging to guide treatment. Early diagnosis and intervention are critical for improving neurodevelopment outcomes.Case Report: A male patient, born at 41 weeks of gestation with a birth weight of 4,400 g (+1.66 SD) and length of 56 cm (+2.0 SD), presented with prolonged neonatal jaundice requiring phototherapy. At six months, episodes of unexplained crying were reported. At one year, he experienced his first seizure episode with upward eye rolling, limb jerking, stiffening, frothy oral secretions, cyanosis, and unresponsiveness followed by fatigue. Hypoglycemia was found during the third seizure (venous glucose: 2.7 mmol/L), prompting further investigation.Admission to pediatric neurology revealed recurrent hypoglycemia on glucose monitoring, with sleep EEG showing no epileptiform activity and brain MRI indicating mild periventricular leukomalacia, linked to prior hypoglycemic episodes.Endocrine evaluation confirmed hyperinsulinemic hypoglycemia: venous glucose: 0.88 mmol/L, insulin: 69.3 mU/L (N: 1.1-17), C-peptide: 2.53 nmol/L (N: 0.23-0.81). Genetic testing revealed a maternally inherited heterozygous pathogenic variant in ABCC8 (NM_001287174.1:c.3992-9G>A). As carriers are typically asymptomatic, insulinoma was considered, but PET/CT with 68Ga-DOTATOC ruled out focal pancreatic lesions.Follow-up testing revealed recurring hypoglycemia despite low insulin (2.4 mU/L) and C-peptide (0.15 nmol/L) levels, necessitating an increase in diazoxide therapy (25 mg three times daily). Despite early neurological impact linked to hypoglycemia, the patient’s neurodevelopment milestones remained appropriate for age.Conclusion: This case underscores the clinical variability of CHI associated with ABCC8 variants, challenging the assumption of asymptomatic carrier status and highlighting the complexity of managing patients with uncertain genetic findings. Evaluating variant pathogenicity alongside clinical presentation remains essential, supported by a comprehensive diagnostic approach involving genetic testing, advanced imaging, and multidisciplinary care to optimize treatment and guide therapeutic strategies. Presentation: Sunday, July 13, 2025