Abstract
Introduction: The serine-threonine kinase AKT2 is a critical
mediator of insulin’s anabolic effects, particularly cellular glucose
uptake. The gain-of-function c.49G>A, p.(Glu17Lys)AKT2 variant results in hypoketotic hypoglycemia with suppressed
insulin and free fatty acid levels due to constitutive activation of the
insulin signaling cascade. Although biochemical similarities exist
amongst the eight individuals identified to date, the associated
phenotype varies considerably. Treatment of these patients remains
challenging, consisting primarily of frequent feeds with uncooked
cornstarch.
Case Presentation: We describe a female with hemihypertrophy,
developmental delay, and dysmorphic features who presented to our center
with hypoglycemic seizures at age 6-months. Critical sample revealed
hypoketotic hypoglycemia, undetectable insulin, and suppressed free
fatty acids. Molecular testing confirmed a pathogenic
c.49G>A, p.(Glu17Lys) AKT2 mutation. Glycemic
control was initially difficult to establish, with recurrent
hypoglycemia despite high glucose infusion rates. Following in-hospital
administration of waxy maize heat-modified starch at age 4-years she
remained euglycemic overnight, despite a previous report showing no
benefit compared to uncooked cornstarch in an infant with the same
mutation.
Conclusion: Our report suggests waxy maize heat-modified starch
is a viable treatment option for patients with activating
c.49G>A AKT2 mutations and provides further evidence
of a broad phenotypic spectrum.
Keywords: hypoglycemia, AKT2, starch
Key Clinical Message: The gain-of-function AKT2c.49G>A variant causes hypoketotic hypoglycemia with
variable associated features. Due to lack of effective medications,
treatment is primarily supportive. This report suggests waxy maize heat
is a viable treatment option.