Facial Dysmorphic Features in a Patient With Nonketotic Hypoglycemia and a Pathogenic Variant in the AKT2 Gene

AKT2 is a serine/threonine kinase that plays a key role in regulating insulin signaling. The phenotype related to the gain-of-function alteration in the AKT2 gene (c.49G>A, p.Glu17Lys) has been described in 5 patients with clinical findings that mimic hyperinsulinemic hypoglycemia but with undetectable levels of insulin and C-peptide. One of the reports highlights the facial dysmorphic features. We report the case of a new patient with the same activating AKT2 alteration leading to autonomous activation of the insulin signaling pathway and dysmorphic features. Moreover, to our knowledge, this is the first report using waxy maize heat-modified starch (WMHMS) in this condition.

A previously healthy child was evaluated at 6 months of age for episodes of hypoglycemia. The laboratory test results for the critical samples showed hypoketotic hypoglycemia (glucose level, 2.16 mmol/L [38 mg/dL]) with undetectable levels of insulin (<0.2 mU/L) and C-peptide (<0.033 nmol/L [reference range, 0.37-1.47 nmol/L]). Physical examination revealed hypertelorism, prominent proptosis of the eyes, a flat nasal bridge, delayed psychomotor development, and postnatal symmetrical overgrowth. The genetic study of AKT2 showed a pathogenic variant (c.49G>A, p.Glu17Lys). To achieve euglycemia, a diet of regular uncooked cornstarch (UCCS) carbohydrate was started. Subsequently, waxy maize heat-modified starch (WMHMS; Glycosade Vitaflo) was used to increase the fasting period to 4 hours. However, we did not find any advantages in comparison with UCCS.

The range of phenotypes of this gain-of-function alteration in AKT2 may be broad, including dysmorphic features, although the patients harbor the same pathogenic variant.

Regarding the treatment, we observed a similar response with WMHMS compared with UCCS, with no adverse effects.