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).

Background Transient neonatal hypoglycemia typically resolves within the first few days of life. Persistence of neonatal hypoglycemia is a more significant finding that warrants further investigation. Clinical case A 2-year-old female born at 37 weeks of gestation via C-section due to a history of maternal preeclampsia. Delivery was complicated by meconium aspiration syndrome for which the patient was admitted to the NICU where she had a prolonged course. Patient was initially depressed at birth with APGARs of 3/6/8 at 1, 5 and 10 minutes of life, respectively. During the neonatal period, she had multiple complications including GERD, FTT (G-tube was placed), recurrent UTIs, congenital heart disease (mild RVH and ASD) and hypoglycemia. Regarding her hypoglycemia, the initial work up was suggestive of hyperinsulinism with a critical sample remarkable for a BG: 57 mg/dl (60-100mg/dl), Insulin level: 8.3 uUm/mL Subsequent glucagon challenge test confirmed hyperinsulinism. She initially required a continuous glucose infusion and Diazoxide was started. She was discharged home on Diazoxide and Diuril. Subsequently, Diazoxide was successfully discontinued at the age of 2 months. A Congenital Hyperinsulinism genetic panel was negative for the most frequent mutations. At 11 months old, she presented to our clinic due to persistent hypoglycemia when enteral feeds were attempted to be spaced. Patient was started on cornstarch which was discontinued secondary to frequent diarrhea. SolCarb was started with enteral feeds with good tolerance and response, maintaining target blood glucose levels. On physical examination, she had some dysmorphic features that were suggestive of a syndromic condition: prominent ear lobes, broad and flat nasal bridge, a single prominent tooth at the center of the bottom gum line, long palpebral fissures with upward curvature at the lateral edges, prominent finger pads and neurodevelopmental delay. Since she had features suggestive of Kabuki syndrome, WES was ordered which was remarkable for a pathogenic mutation in KMT2D (Autosomal dominant, Heterozygous, variant c.5269C>T and p.R1757X). Conclusion Persistent hypoglycemia beyond the neonatal period is a rare finding in Kabuki syndrome. In addition, it is a more common finding in Kabuki Syndrome type 2 (Mutations in the KDM6A gene). Our patient presents a rare case of a 2-year-old female with persistent hypoglycemia and hyperinsulinism secondary to KS1. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.