A standard dose glucagon challenge was performed immediately following critical sample collection, resulting in an increase in bedside capillary glucose from 1.9 mmol/L to 4.4 mmol/L. This is in keeping with hyperinsulinism, as an increment of at least 1.7 mmol/L suggests suppression of hepatic glycogenolysis by excess insulin.¹⁰ Given this glucagon response and hypoketotic hypoglycemia, a presumptive diagnosis of congenital hyperinsulinism was made. Although not initially available, the serum free fatty acid level returned suppressed at 227 umol/L, further supporting the initial diagnosis.

Initial stabilization was achieved with a bolus of 10% dextrose followed by continuous infusion. Despite GIR exceeding 15 mg/kg/min, she experienced recurrent episodes of hypoglycemia requiring repeated boluses of 10% dextrose. The insulin level subsequently returned undetectable, with no evidence of hemolysis or sample degradation causing an artifactual reduction in measured insulin. Octreotide and diazoxide were separately trialed given her persistent hypoglycemia and biochemical profile otherwise suggestive of hyperinsulinism. She was unable to tolerate a wean of intravenous dextrose or pauses in the infusion exceeding 30 minutes, despite octreotide doses of up to 20 ug/kg/day or diazoxide of 15mg/kg/day. Both medications were eventually discontinued, and she successfully transitioned to continuous nasogastric feeds providing a GIR of 13 mg/kg/min before discharge home.

Given the severity and persistence of hypoglycemia, a comprehensive panel for genes implicated in hypoglycemia, hyperinsulinemia, and ketone metabolism was performed on peripheral blood leukocytes. This demonstrated a pathogenic heterozygous variant in AKT2,c.49G>A, p.(Glu17Lys) previously reported in other individuals with gain-of-function AKT2variants.^4-8 To assess for possible mosaicism, DNA from skin fibroblasts was subsequently analyzed and found to be positive for the mutation.

Based on the glucose requirements reported in other cases,⁷ feeds were changed to three times daily followed by uncooked cornstarch at 1.5-2 g/kg to maintain euglycemia between feeds, in addition to an overnight continuous feed which provided an overall GIR of 4-5 mg/kg/min. More recently, a 4.3 g/kg dose of WMHMS (1.5 packets of Glycosade, Vitaflo USA, NJ) was trialed in hospital with successful maintenance of overnight euglycemia without the addition of a continuous feed (Figure 2).