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).