SUN-207 Hyperinsulinemia in Atypical Fanconi Syndrome with Elevated Transaminases

Abstract Disclosure: N. Solano: None. F. Ramirez-Seijas: None. A. Diaz: None. We present the case of a 4-year-old boy from South America, who was initially found to have glucosuria during a routine urinalysis at 1 year of age. Further evaluation revealed renal tubular acidosis, proteinuria, glucosuria, hypercalciuria, and nephrocalcinosis. Notably, he was found to have hypoglycemia with an inappropriately elevated insulin level during his work-up. He was started on sodium bicarbonate and citrate and referred to our institution for additional evaluation. His past medical history included being born at 35 weeks gestation, with a birth weight and length at the 5th percentile and a target height at the 25th percentile. He also had a delay in speech development. Upon first evaluation at our institution at 2.5 years of age, his height was at the 5th percentile, and his BMI was at the 50th percentile. Fasting glucose levels were low, accompanied by inappropriately elevated insulin levels and suppressed beta-hydroxybutyrate levels. Based on these findings, genetic testing for HNF4A was performed, revealing a pathogenic heterozygous mutation: c.187C>T (R85W), p.Arg63Trp (this mutation has also been reported as p.Arg76Trp [p.R76W], c.226C>T). The child was subsequently started on diazoxide at 10 mg/kg/day, divided into three doses, leading to an immediate improvement in glucose levels. Additionally, it was noted that his transaminases had been consistently elevated at twice the normal value. Several cases have been reported of patients with HNF4A mutations presenting with transient or persistent hyperinsulinism, some of which later develop diabetes around a median age of 24 years. A 2013 report described six patients from the UK with Fanconi syndrome and neonatal hyperinsulinemia caused by the same heterozygous HNF4A mutation. Two of these patients developed diabetes mellitus at ages 12 and 20. Additionally, we identified three other reports involving four children with the same heterozygous HNF4A mutation. In two of these patients, hepatomegaly with elevated transaminases was observed. However, hepatomegaly was not noted in our patient. To our knowledge, our patient is one of the few cases reported with this specific HNF4A mutation. This patient presented with an atypical form of Fanconi syndrome, characterized by elevated transaminases and hypoglycemia due to hyperinsulinemia, which responded to diazoxide treatment. Presentation: Sunday, July 13, 2025