SUN-206 Unique Case of an 11-Year-Old Boy With Donohue Syndrome

Abstract Disclosure: M. Giraldo: None. C.M. de Almagro: None. A. Carrillo-Iregui: None. L.E. Gonzalez-Mendoza: None. Introduction: Donohue Syndrome is a rare autosomal recessive disorder caused by mutations in the INSR gene, impairing insulin receptor function. The pathogenic variant causes severe hyperinsulinemia with high plasma insulin and c-peptide levels with fluctuating blood glucose levels. Also known as “Leprechaunism” due to its phenotypic presentation, the prevalence is rare with less than 1 case per million births: occurring more frequently in females than in males. It is characterized by severe insulin resistance, prenatal growth restriction followed by postnatal growth failure, hypotonia, developmental delay, dysmorphic facial features (gingival hypertrophy, large low-set ears, infraorbital folds, thick vermillion of upper and lower lips), hypertrichosis, and organomegaly. This syndrome has a poor prognosis of approximately 1 year of life. Case Report: We present a case of a now 11-year-old male who was initially consulted at birth due to hyperglycemia. Patient was born at 35 weeks gestation with prenatal history of asymmetric intrauterine growth restriction (IUGR) and preeclampsia. At initial assessment patient with dysmorphic features (large lips, small chin), hepatomegaly, hypertrichosis, significantly elevated insulin levels (83.1 uIU/mL to 100.8 uIU/mL) and fluctuating blood glucose levels (37-233 mg/dL) within the first two weeks of birth. Diagnosed with INSR mutation c.1610+2T>C, amino acid change. During admission for one-month post-birth, patient had persistent hyperglycemia only responsive to insulin drip. He did not respond to high-dose Lantus. Patient was discharged home on feedings every 3 hours. Eventually, patient was managed only with a limited carbohydrate intake of 30% of caloric intake (56g formula + 40-45g solid food) with no required insulin. Insulin level ranging from 341uIU/mL to 1,368 uIU/mL. Most recent bone age read as 6 years old, while patient’s chronological age is 8 years and 3 months. Patient’s height -4.38 SDS with BMI within the 68th percentile (0.47 SDS). Conclusion: We report a rare presentation of Donohue Syndrome in a male patient, illustrating the early onset of severe hyperinsulinemia as well as the dysmorphic facial characteristics, hepatomegaly, and significant growth restriction. Genetic testing confirmed a pathogenic INSR mutation. Management focused on strict monitoring of glucose levels and a specialized diet. This is a notable case as patient has overcome the poor life expectancy of this syndrome despite significant failure to thrive. The absence of effective pharmacologic therapies for insulin resistance highlights the need for individualized management, incorporating dietary modifications and continuous glucose monitoring. Early recognition and genetic testing in neonates are crucial for optimizing care and addressing the complexities of this syndrome. Presentation: Sunday, July 13, 2025