Successful Use of Intragastric Dextrose in a Unique Presentation of Congenital Hyperinsulinism

Introduction: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and can pose challenges if unresponsive to diazoxide. HI can be caused by monogenic mutations or can be associated with genetic syndromes. Macrocephaly Capillary malformation (MCAP) is a rare overgrowth syndrome, caused by heterozygous variants in the PIK3CA gene. A small number of pathologic variants in this gene have been reported to cause HI. Clinical Case: A 4-month-old boy presented with a hypoglycemic seizure while fasting for an MRI. His history was notable for being born LGA and having macrocephaly, segmental infantile hemangioma, and ventriculomegaly requiring VP shunt. Critical labs were consistent with HI: plasma glucose (PG) of 23 mg/dL (54-117), inappropriately detectable insulin (2.7 mIU/mL) and c-peptide (1.6 ng/mL), low beta hydroxybutyrate (0.1 mmol/L) and low free fatty acids (0.16 mmol/L), and a positive glucagon stimulation test (increase in PG from 48 to 101 mg/dL in 30 minutes). Diazoxide was started at 5 mg/kg/day and titrated to 15 mg/kg/day, but he was unable to maintain PG >70 mg/dL. He was deemed unresponsive and the diazoxide was discontinued. His intravenous glucose infusion rate (GIR) was 14.4 mg/kg/min. An octreotide trial (8 mcg/kg/day) revealed a robust response: PG 64 mg/dL before initial dose, 105 mg/dL 3 hours later. However, he developed tachyphylaxis to the octreotide and it was discontinued. To further evaluate the etiology of his HI, he underwent an (18)F-DOPA PET scan, which showed diffuse uptake. Genetic sequencing for the 9 known HI genes was negative. At 6-months-old, he was evaluated by genetics who based on his clinical features diagnosed him with MCAP. After failure of diazoxide and octreotide therapies, he was slowly transitioned from IV dextrose to continuous intragastric dextrose (IGD) using D20W. He was managed with a GIR of 10 mg/kg/min during the day (while receiving bolus feeds) and 5 mg/kg/min while on continuous feeds overnight. The continuous IGD allowed him to maintain euglycemia and develop his oral feeding skills. By 17-months-old, feeds by mouth improved and GIR had decreased to 6.5 mg/kg/min during the day and 2.5 mg/kg/min overnight. Genetic analysis eventually revealed a heterozygous p.Glu365Lys (c.1093 G>A) variant in the PIK3CA gene as the likely cause of the HI. Conclusion: Genetic syndromes should be considered in infants with persistent hyperinsulinism and multiple congenital anomalies. Clinical work-up may provide important clues to the diagnosis. Diazoxide unresponsive HI can be treated with continuous IGD to prevent hypoglycemia-induced brain damage. Continuous IGD likely leads to better oral skills and decreased oral aversion compared to using continuous formula feeds.