SI Institute of Hereditary Pathology NAMS of Ukraine, Lviv, Ukraine.
Department of Paediatrics, Medical University of Warsaw, Warsaw, Poland.
Eur J Med Genet. 2021 Dec;64(12):104368. doi: 10.1016/j.ejmg.2021.104368. Epub 2021 Oct 18.
Activating mutation in the insulin signal-transducing kinase AKT2 results in severe hypoinsulinemic hypoketotic hypoglycemia and a characteristic phenotype of possible overgrowth and, sometimes, acanthosis nigricans. Herein, we describe a metabolic and hormonal profile before and during treatment with sirolimus in two brothers with AKT2 mutation inherited from the mosaic father, who showed low-level mosaicism in sperm. The boys, aged 1 and 14, who had severe non-insulin-dependent hypoketotic hypoglycemia and a typical dysmorphism, were admitted to endocrinology department for the analysis of their metabolic parameters: lipids, lactate, ammonia, glucose, insulin, c-peptide, and hormones (GH, IGF1, IGFBP3, TSH, fT4, cortisol, ACTH) before and during treatment with sirolimus. Previously, they had been treated with high-carbohydrate diet. The brothers were started on sirolimus with subsequent normalization of glycemia and reduced carbohydrate feedings overnight. The lowest fasting glucose levels improved from 20 mg/dl to 45 mg/dl in both sibs. The BMI of both brothers significantly dropped. After 6 months of sirolimus therapy we did not observe any laboratory or clinical side effects of the treatment.
胰岛素信号转导激酶 AKT2 的激活突变导致严重的胰岛素缺乏性低血糖伴酮血症和可能过度生长的特征表型，有时还伴有黑棘皮病。在此，我们描述了两个男孩在接受西罗莫司治疗前后的代谢和激素特征，他们均从嵌合父亲那里遗传了 AKT2 突变，而父亲的精子中存在低水平的嵌合现象。这两个男孩一个 1 岁，一个 14 岁，患有严重的非胰岛素依赖性低血糖伴酮血症和典型的畸形，他们因代谢参数分析而被收入内分泌科：治疗前后的血脂、乳酸、氨、血糖、胰岛素、C 肽和激素（GH、IGF1、IGFBP3、TSH、游离 T4、皮质醇、ACTH）。此前，他们接受了高碳水化合物饮食治疗。随后，我们给两个男孩都使用了西罗莫司，之后他们的血糖恢复正常，夜间碳水化合物摄入量减少。两个孩子的空腹血糖水平从 20mg/dl 改善到 45mg/dl。两个兄弟的 BMI 均显著下降。西罗莫司治疗 6 个月后，我们未观察到任何治疗相关的实验室或临床副作用。
