Abstract #1412358: A Case of Neonatal Diabetes

Abstract

Neonatal diabetes is a term commonly used to describe the different forms of monogenic diabetes that present in infancy. The average time of presentation is within six months of age however it can present up to 12 months of age. This contrasts to type 1 diabetes which rarely presents within the first six months of life. The incidence of neonatal diabetes is estimated to be 1 in 90,000 to 160,000 live births. There have been over 30 genetic mutations identified that affect pancreatic beta cell function. The phenotypic expression of these mutations varies from transient diabetes (20% of cases), to diabetes responsive to sulfonylurea (40% of cases), to permanent diabetes requiring lifelong insulin therapy (10% of cases), to syndromic and autoimmune diabetes with extra pancreatic features. Here we present a case of neonatal diabetes secondary to a KCNJ11 mutation being treated with sulfonylurea. A 24-year-old male with a past medical history of diabetes mellitus diagnosed at three months of age, behavioral disorders and developmental delay is being managed in Endocrinology clinic for uncontrolled diabetes complicated by multiple admissions with diabetic ketoacidosis. He has a family history of type 2 diabetes in his father. The patient was initially diagnosed and treated as a type I diabetic until at ten years of age genetic testing confirmed a heterozygous R201C mutation of the KCJN11 gene consistent with the diagnosis of neonatal diabetes. He was successfully switched from insulin to high doses of glyburide including 50mg with breakfast, 50mg with dinner, and 30mg at bedtime. The hemoglobin A1c ranged 11-12% due to issues with non-adherence, so Tresiba 22 units at bedtime was added. At the age of 19, the patient transferred care to adult Endocrinology. His exam was remarkable for a BMI of 23 and difficulty with serial seven count down and five-word recall. Relevant labs included c-peptide < 0.1, negative GAD65 Ab, A1c 13%. After an admission for DKA, the patient was prescribed Glargine 28 units daily and Humalog 20 units before meals. Due to difficulty titrating and adhering to this insulin regimen, he was recently restarted this year on glyburide 50mg twice a day with Tresiba 15 units at bedtime with plan to titrate up the doses of the sulfonylurea and discontinue insulin. Mutations in KCNJ11 and ABCC8 are the most common affecting around 46% of infants with neonatal diabetes. They encode for subunits of the ATP-sensitive potassium channel (KATP), which affects the membrane depolarization required for insulin exocytosis in the pancreatic beta cell. Infants with these mutations may also present with varying degrees of neurodevelopmental and psychiatric problems due to presence of KATP channels in the brain. Early treatment with sulfonylurea may improve neurologic outcomes. It is estimated that 80-90% of patients with these mutations will respond to sulfonylurea treatment with high doses of glyburide (up to 2.5mg/kg per day) and eliminate the need for insulin, while 10% may not respond and may still need insulin.