Introduction
Insulin’s crucial role in energy metabolism is coordinated by a
post-receptor signaling cascade resulting in activation of Akt2, a
serine-threonine kinase. Expressed predominantly in insulin-sensitive
tissue, Akt2 promotes glucose uptake by regulating translocation of the
glucose transporter-4 (GLUT4) from cytoplasm to the cell
membrane.1 Further, Akt2 mediates insulin’s metabolic
effects by suppressing gluconeogenesis1 and
lipolysis2, and stimulating
lipogenesis.3
A growing body of evidence supports the clinical relevance of AKT2.
Although rare, gain-of-function mutations in AKT2 have been
described in eight individuals with hypoketotic
hypoglycemia.4-8 Despite undetectable insulin levels,
their biochemical profiles closely resemble hyperinsulinemic
hypoglycemia due to constitutive activation of the insulin signaling
cascade. Additional reported features include accelerated linear growth,
hemihypertrophy, and polyhydramnios.4,6 Other features
have been variably reported including characteristic facies, acanthosis
nigricans, developmental delay and intellectual
disability.5,6
Given the detrimental neurodevelopmental impact of hypoglycemia in
infancy and childhood, achieving euglycemia is critical. Management
consists of frequent carbohydrate-rich feedings, often including
uncooked cornstarch.5 However, with this approach,
euglycemia is achieved at the expense of excess weight gain and impaired
quality of life.7 Due to the anticipated lifelong
duration of treatment, alternate therapeutic approaches are needed. An
encouraging option is modified waxy maize heat modified starch (WMHMS)
which demonstrates improved tolerability and longer duration of action
than uncooked cornstarch.9
We report a patient with an activating AKT2 mutation managed with
WMHMS, providing additional insight into the phenotypic spectrum.