A 13-Year-Old Girl with Congenital Hyperinsulinemic Hypoglycemia Due to an ABCC8 Mutation and Recent Onset of Diabetes Mellitus: A Case Report and Literature Review.

Abstract

Congenital hyperinsulinism (HI) is the most prevalent cause of persistent hypoglycemia in infancy and childhood and comprises a heterogeneous group of genetic disorders affecting insulin secretion. The most common etiology involves inactivating mutations in the ABCC8 and KCNJ11 genes, which encode the SUR1 and Kir6.2 subunits of the pancreatic β-cell ATP-sensitive potassium (KATP) channel. Variants in these genes are associated with a broad phenotypic spectrum, ranging from asymptomatic macrosomia and mild diazoxide-responsive disease to severe, persistent hyperinsulinemic hypoglycemia unresponsive to medical therapy. In some individuals, the clinical course may evolve over time, with progression from early hyperinsulinism to impaired glucose regulation and eventual diabetes mellitus. We describe a 13-year-old girl with diazoxide-unresponsive congenital hyperinsulinism caused by a heterozygous de novo ABCC8 variant (c.2147G>A, p.Gly716Asp) who later developed insulin-deficient diabetes mellitus. She was treated with octreotide from 2 months until 7 years of age, when therapy was discontinued after gradual remission of hypoglycemia. At 11 years, evaluation revealed impaired fasting glucose and impaired glucose tolerance, and glibenclamide was initiated. After being lost to follow-up, she presented at 13 years with hyperglycemia and was diagnosed with antibody-negative, insulin-deficient diabetes mellitus. Basal insulin therapy led to progressive normalization of glycemic levels. To our knowledge, this is the first report linking the ABCC8 p.Gly716Asp variant to transition from congenital hyperinsulinism to adolescent-onset diabetes, underscoring the phenotypic continuum of ABCC8-related disorders and the necessity for lifelong metabolic surveillance.