Arya Ved Bhushan, Flanagan Sarah E, Schober Edith, Rami-Merhar Birgit, Ellard Sian, Hussain Khalid
London Centre for Paediatric Endocrinology (V.B.A., K.H.), Great Ormond Street Hospital for Children National Health Service Foundation Trust, London WC1N 3JH, United Kingdom; The Institute of Child Health (V.B.A., K.H.), University College London, London WC1N 1EH, United Kingdom; Institute of Biomedical and Clinical Science (S.E.F., S.E.), University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Department of Pediatrics (E.S., B.R.-M.), Medical University of Vienna, 1090 Vienna, Austria.
J Clin Endocrinol Metab. 2014 Feb;99(2):391-4. doi: 10.1210/jc.2013-3228. Epub 2013 Nov 27.
Hyperinsulinemic hypoglycemia (HH), characterized by unregulated insulin secretion, is an important cause of persistent and severe hypoglycemia. The biochemical picture of HH is hypoketotic hypo-fatty-acidemic hypoglycemia along with elevated serum insulin. Not infrequently, serum insulin might be undetectable in HH despite the presence of evidence of insulin action (suppressed ketogenesis and lipolysis). However, autonomous activity of the downstream insulin signaling pathway without the presence of the ligand (insulin) will give rise to the same clinical and biochemical picture, apart from undetectable serum insulin/C-peptide. AKT2, a serine/threonine protein kinase, is involved downstream to the insulin receptor in mediating the physiological effects of insulin.
We describe the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypoglycemia.
The proband presented with hemihypertrophy and symptomatic hypoglycemia. Investigations confirmed evidence of insulin action, despite absence of detectable serum insulin on multiple occasions. Molecular genetic testing for common causes of HH (ABCC8, KCNJ11, and GLUD1) was negative. Sequencing of AKT2 identified a de novo mosaic c.49G→A (p.E17K) mutation, consistent with the clinical and biochemical phenotype.
This is the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypo-fatty-acidemic hypoglycemia. In patients presenting a clinical and biochemical picture of HH with undetectable serum insulin, consideration of autonomous activation of the downstream insulin signaling pathway should be made.
高胰岛素血症性低血糖症（HH）以胰岛素分泌失调为特征，是持续性严重低血糖的重要原因。HH的生化表现为低酮血症性低脂肪酸血症性低血糖伴血清胰岛素升高。尽管存在胰岛素作用的证据（酮生成和脂肪分解受抑制），但在HH患者中血清胰岛素常常检测不到。然而，在没有配体（胰岛素）的情况下，下游胰岛素信号通路的自主活性会导致相同的临床和生化表现，只是血清胰岛素/C肽检测不到。AKT2是一种丝氨酸/苏氨酸蛋白激酶，在胰岛素受体下游参与介导胰岛素的生理作用。
我们描述了第二例由激活型AKT2突变导致低胰岛素血症性低酮血症性低血糖症的报告。
先证者表现为半身肥大和症状性低血糖。尽管多次检测不到可检测的血清胰岛素，但检查证实了胰岛素作用的证据。对HH常见病因（ABCC8、KCNJ11和GLUD1）的分子遗传学检测为阴性。对AKT2进行测序发现了一个新发的嵌合型c.49G→A（p.E17K）突变，与临床和生化表型一致。
这是第二例由激活型AKT2突变导致低胰岛素血症性低酮血症性低脂肪酸血症性低血糖症的报告。对于呈现HH临床和生化表现且血清胰岛素检测不到的患者，应考虑下游胰岛素信号通路的自主激活。
