A Very Rare Case of Diabetes Mellitus Occurring in a Patient With Hyperinsulinism Hyperammonemia Syndrome.

Background/Objective: To illustrate an unusual case of type 2 diabetes mellitus (T2DM) developing many years after the diagnosis of hyperinsulinism hyperammonemia (HI/HA) syndrome. Case Report: This article reports about a 36-year-old female with a history of congenital hyperinsulinism due to HI/HA syndrome, which was diagnosed in infancy. The patient presented with hypoglycemia and seizures as an infant and was treated with diazoxide and a low-protein diet for many years with reduction in her hypoglycemic events. She subsequently developed T2DM >30 years later. Genetic analysis was positive for a glutamate dehydrogenase 1 gene (GLUD1) alteration. She was treated with metformin and a glucagon-like peptide 1 agonist, with significant improvement in her blood glucose control and weight loss. Discussion: HI/HA syndrome is a rare genetic syndrome that manifests in childhood with signs and symptoms of hypoglycemia and neurologic symptoms. This is the first case reported in the literature of a patient with HI/HA syndrome due to a GLUD1 alteration who developed T2DM much later in life. Patients with this disorder usually have recurrent hypoglycemia and require long-term medical therapy or very occasionally may have a resolution. She had class 3 obesity and evidence of insulin resistance, which likely contributed to her risk of diabetes. Conclusion: This is a rare case of T2DM presenting in a patient with HI/HA syndrome. This should be considered a possible outcome in patients with this disorder, especially in the presence of obesity.