Persistent Hypoglycemia and Hyperinsulinism in a Patient With KMT2D- Associated Kabuki Syndrome

Abstract

We report a 3-year-old girl with persistent hypoglycemia and hyperinsulinism secondary to KMT2D-associated Kabuki syndrome (KS). During the neonatal period, the patient had multiple complications, including gastroesophageal reflux disease, failure to thrive, G-tube dependence, congenital heart disease, and persistent hypoglycemia. The initial workup at 2 weeks of age was suggestive of hyperinsulinism. She was treated with intravenous glucose infusion and diazoxide. She was discharged from the NICU on diazoxide, chlorothiazide, and enteral feeds. Diazoxide was discontinued at 2 months old secondary to adverse effects. Hyperinsulinemic hypoglycemia was ultimately confirmed with a glucagon stimulation test at 5 months of age. At 11 months of age, when the enteral feeds were attempted to be spaced, she presented to our outpatient clinic with persistent hypoglycemia. Review of prior outside records confirmed a negative congenital hyperinsulinism genetic panel. She was treated with maltodextrin, enteral feeds, and close glucose monitoring. We noted that she had dysmorphic features that were suggestive of KS. At 2 years of age, a whole exome sequence confirmed a pathogenic mutation in KMT2D. Persistent hypoglycemia beyond the neonatal period is a rare finding in KS. In addition, it is a more common finding in KS type 2 (KDM6A).

Keywords: KMT2D; Kabuki syndrome; hyperinsulinism; hypoglycemia.