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Abstract Disclosure: E.E. Bell-Sambataro: None. L. Mamilly: None. Background: Congenital hyperinsulinism (CHI) is characterized by inappropriate secretion of insulin during periods of low blood glucose. CHI can lead to significant complications such as seizures, developmental delays and neurologic damage. CHI can be caused by multiple genetic variants. The most common genetic etiologies are loss of function mutations in the genes ABCC8 and KCNJ11 encoding the pancreatic Beta (β)-cell ATP-sensitive potassium channel causing over secretion of insulin from the β-cells. We report a challenging pediatric case with a clinical presentation of CHI in an infant with a de novo mosaic ABCC8 gene variant of unknown significance manifesting only during times of illness. Clinical Case: A male infant born at 36 weeks gestational age was transferred to a tertiary center NICU secondary to seizure activity and hypoglycemia after the 24 hours of life with glucose levels as low as 32 mg/dL. His birth weight was normal and there was not maternal history of diabetes mellitus. The hypoglycemia persisted throughout the first week of life and required a glucose infusion rate of 11 mg/kg/min, without success in obtaining a critical sample. He had multiple seizures and MRI brain showed signs of hypoglycemic encephalopathy. Subsequently, he was weaned off IV dextrose and completed a 6 hour safety fast prior to discharge. Rapid genome testing resulted in a de novo, mosaic variant of unknown significance in ABCC8 (C.3622GA resulting in amino acid substitution p.Glu1208Lys). His family reported significant but transient hypoglycemia during times of illness. At the age of 11 months, he was hospitalized for significant hypoglycemia during an episode of acute gastroenteritis and was treated with dextrose-containing fluids for 36 hours. A subsequent diagnostic fasting study resulted in hypoglycemia within 5.5 hours with capillary glucose of 49 mg/dL. At the time of hypoglycemia, beta hydroxybutyrate was inappropriately low at 0.78 mm, insulin level was suppressed 2 mcIU/mL. Glucagon (30 mcg/Kg) was administered after the initial sample was drawn with a significant increase in glucose from 49 mg/dL to 103 mg/dL. Based on the positive glucagon response and low serum ketone, the clinical diagnosis of CHI was made and diazoxide was initiated while awaiting other results. After the second dose of diazoxide, all glucose levels remained above 80 mg/dL. He was sent home on a continuous glucose monitor and diazoxide. Conclusion: CHI can occur due to autosomal recessive or autosomal dominant ABCC8 loss-of-function mutations of which more than half are not responsive to diazoxide. In this case report, we describe the diagnosis of hyperinsulinemic hypoglycemia in an infant with an ABCC8 variant classified with unknown significance. We describe a good initial response to diazoxide in normalizing blood glucose levels in this infant. Presentation: 6/2/2024
Bell-Sambataro et al. (Tue,) studied this question.