SAT086 Early-onset HNF1B-MODY With Persistent Insulin Requirement In A 2-year-old Female

Abstract

Abstract Disclosure: F. Ighalo: None. S.R. Kelly: None. M. Tosur: None. M.E. Craven: None. Introduction: Diabetes related to HNF1B pathogenic variants or deletions (maturity-onset diabetes of the young 5 [MODY 5]) typically presents in adolescence or early adulthood, with a median age of 20 years. Bustamante et al. previously described two patients with 17q12 deletion encompassing HNF1B presenting with diabetes and pre-diabetes before the age of 3, who were managed with dietary intervention alone without insulin requirement. This case describes a 2-year-old diagnosed with HNF1B-MODY after developing hyperglycemia in the setting of an acute illness, who continued to require insulin therapy following recovery. Clinical Case: A 2-year-old female with a history of recurrent viral infections and failure to thrive was admitted to the intensive care unit in hypovolemic shock due to hemolytic uremic syndrome due to Shiga toxin. On hospital day 7, while on supraphysiologic steroid doses, she developed hyperglycemia with glucoses above 600 mg/dL. She required an insulin drip to maintain blood glucoses between 100 and 200 mg/dL. Her four-month hospital stay was complicated by cardiogenic shock requiring extracorporeal mechanical oxygenation, renal failure requiring hemodialysis, respiratory failure resulting in a tracheostomy, and dysphagia resulting in a gastrostomy tube. During this time, she continued to require insulin despite being weaned off steroids and transitioning from total parenteral nutrition to gastrostomy tube feeds. Her hemoglobin A1c one month post-diagnosis was 4.9%, and continued to rise to 6.6% and 7.6% at 3 and 4 months post-diagnosis, respectively. Testing for islet autoantibodies was negative. A chromosomal microarray analysis revealed a micro-deletion in chromosome 17q12 that included the HNF1B gene. MRI showed a near total absent pancreas, and multiple small cysts scattered throughout both kidneys. She also had fecal elastase levels in the insufficient range (135 mcg/g, normal >200 mcg/g). Six weeks after the start of insulin drip, she was transitioned from an insulin drip to subcutaneous insulin injections, and eventually placed on an insulin pump prior to discharge. With continued clinical improvement, her insulin doses decreased, but she was not able to come off insulin completely. She had gradual decline in her insulin requirements from 1.0 units/kg/day down to 0.1 units/kg/day at time of discharge. Her current insulin requirement at 6 months post-diagnosis is 0.2 units/kg/day. Conclusion: This case represents the rare development of diabetes before adolescence in HNF1B-MODY, and one of the most severe presentations seen in a prepubertal child requiring persistent insulin therapy at 6 months post-diagnosis. Potential contribution of complicated hospital course on persistent insulin requirement in the setting of 17q12 micro-deletion cannot be excluded. Presentation: Saturday, June 17, 2023