SUN-631 Hyperinsulinism/Hyperammonemia (HI/HA); A Rare Endocrine Disorder

Abstract Disclosure: S. Keritum: None. T. Altaweel: None. Z.M. Albahbahanee: None. W. Taha: None. IntroductionHyperinsulinism/Hyperammonemia (HI/HA) syndrome is characterized by hypoglycemia triggered by high-protein diet and elevated serum ammonia level. It results from a gain of function mutations in the glutamate dehydrogenase-1 (GLUD1) gene encodes glutamate dehydrogenase (GDH) enzyme. The incidence is 1 in 28,000 to 50,000 live births in the general population. Children develop seizures, learning difficulties and behavioral issues, including attention deficit hyperactivity disorder (ADHD).Case presentationWe are presenting a 34-year-old female with a medical history of developmental delay and seizures, diagnosed with HI/HA syndrome at 3 months of age and is currently receiving treatment with Diazoxide and Keppra. The patient was hospitalized for recurrent, intractable complex partial seizures. The patient’s vitals were normal during her follow up visits, her body mass index range (BMI) 30-35 Kg/m2, random blood glucose level range 60-110 mg/dl, hemoglobin A1c range 4.8-5.5 mg/dl and plasma ammonia level range 225-305 ug/dl.DiscussionInsulin secretion by pancreatic beta cells is initiated when plasma glucose levels rise above 85 mg/dL. Glucose enters the beta cells, metabolized to produce adenosine triphosphate (ATP). The increase in ATP/ADP ratio causes the potassium (KATP) channels to close, leading to membrane depolarization, opening of calcium channels, and increase in intracellular calcium triggering insulin release. In HI/HA syndrome, activating mutation occurs in the gene encoding GDH enzyme in the pathway for amino acid-stimulated insulin secretion, leads to hypoglycemia triggered by protein intake.The presentation of H/HA occurs at birth as hypoglycemia that requires a high glucose infusion rate, plasma ammonia level elevated three to five times the upper limit of normal. Infants should undergo evaluation involving the collection of a "critical sample" during hypoglycemia. Laboratory findings include detectable insulin and C-peptide levels, suppressed beta-hydroxybutyrate (BHB) level <1.8 mmol/L and free fatty acids (FFA) level<1.7 mmol/L.Diazoxide is initially developed for severe hypertension was found to be diabetogenic, it inhibits insulin release, increases glucose level by blocking the sulfonylurea receptor 1 (SUR1) subunit of the KATP channel, enhancing potassium ion permeability, leading to cell hyperpolarization and inhibition of calcium-dependent insulin secretion.ConclusionThis case highlights the clinical presentation of HI/HA syndrome. The patient’s response to diazoxide emphasizes its role in controlling hyperinsulinemic hypoglycemia. Careful management of diet is essential to mitigate protein-induced hypoglycemia. This case underscores the importance of early diagnosis and treatment strategies in improving patient outcomes Presentation: Sunday, July 13, 2025