MON-218 Hyperinsulinemia and MODY 1: Prolonged Neonatal Hypoglycemia Due to MODY Type 1 Pathogenetic Gene Mutation

Abstract Disclosure: L.G. Nasr: None. R. Senguttuvan: None. N. Mitre: None. F.J. Al Muhaisen: None. Background: MODY type 1, driven by pathogenic HNF4A mutations, represents a rare and intriguing form of monogenic diabetes. It is marked by early-onset hyperglycemia, a strong familial inheritance, and a remarkable response to sulfonylureas. Clinical Case: We present the case of a 15-month-old girl born at 37 weeks of gestation to a mother with uncontrolled gestational diabetes managed with long- and short-acting insulin. The pregnancy was complicated by polyhydramnios and circumvallate placenta. Delivered via cesarean section due to her large for gestational age (LGA) status, the patient required NICU admission for respiratory distress and persistent hypoglycemia. Initial stabilization included stimulation, oxygen, gastric suctioning, and a face mask via CPAP. On day one of life, the patient developed low BG down to 11 mg/dlL(n: 60-110mg/dL). Critical blood sampling revealed a serum glucose level of 46 mg/dL (n: 60-110mg/dL), a markedly elevated insulin level of 95 µIU/mL (n: 2-23 µIU/mL), a cortisol level of 1 µg/dL (n: 3-17 µg/dL), and beta-hydroxybutyrate of 0.07 mmol/L (n: 0.02-0.27 mmol/L).The infant was started on IV fluids. Due to persistent hypoglycemia, Fluids and dextrose were advanced. Her GIR was increased to 16.93 mg/kg/min. Enteral feeds were started, and volumes were advanced. Feeds were fortified up to 24 cal/oz to keep glucose above 70 mg/dL.A fasting challenge was done at one month of age and her blood glucose droped below 50 mg/dL by the fourth hour, with critical results showing an insulin level of 16 µIU/mL, cortisol of 13 µg/dL, and beta-hydroxybutyrate of 0.07 mmol/L. Treatment with diazoxide at 5mg/kg/day and chlorothiazide at 5mg/kg/day stabilized blood glucose levels between 70-80 mg/dL. The patient passed a safety fasting challenge before discharge. The patient was seen for follow-up, and at 12 months of age, she continued to need diazoxide treatment. Given the persistent need for diazoxide to maintain stable glucose levels, a hyperinsulinism genetic panel was conducted, identifying a heterozygous pathogenic variant in the HNF4A genec.932G>A(p.Arg311His). This finding confirmed the diagnosis of autosomal dominant HNF4A-related disease, a condition associated with MODY type 1 and neonatal hyperinsulinism, transitioning over time to early-onset diabetes. Conclusion: The identified mutation highlights the unique biphasic clinical course of HNF4A-related disease, where neonatal hyperinsulinism often resolves at 12-18 months of age but predisposes affected individuals to metabolic challenges later in life. This case underscores the critical role of genetic testing in persistent neonatal hypoglycemia to identify monogenic causes, enabling early diagnosis and personalized treatment strategies. Additionally, it emphasizes the importance of long-term follow-up and tailored management to address the evolving clinical manifestations of the disease. Presentation: Monday, July 14, 2025