Hyperinsulinism-hyperammonemia syndrome due to an autosomal dominant GLUD1 p.Ile497Met mutation

Hyperinsulinism-hyperammonemia (HI/HA) syndrome is a rare metabolic disorder caused by mutations in GLUD1, which encodes the mitochondrial enzyme glutamate dehydrogenase (GDH). This condition is characterized by recurrent hypoglycemia, elevated plasma ammonia, and potential neurological complications. We report the case of a 12-month-old male who presented with episodic hypoglycemia, hyperammonemia, and seizures. Family history was notable for childhood-onset hypoglycemia and seizures in the patient's mother and sister. The patient's laboratory findings during hospitalization were significant for markedly elevated C-peptide level of 4.9 ng/mL (SI: 1.63 nmol/L) (reference range; 1.1-4.4 ng/mL [SI: 0.36-1.46 nmol/L]). Insulin was inappropriately detectable at 20.2 µIU/mL (SI: 124.92 pmol/L) during hypoglycemia (reference range; 4.00-30.00 µIU/mL [SI: 24.0-180.0 pmol/L]). Genetic testing identified c.1491A>G (p.Ile497Met) in GLUD1. Following initiation of diazoxide therapy, he experienced symptomatic improvement with a marked reduction in hypoglycemic episodes. This case expands the literature on autosomal dominant HI/HA syndrome associated with an inherited GLUD1 p.Ile497Met mutation.