The Children's Hospital of Philadelphia, Division of Endocrinology and Diabetes, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA.
Rev Endocr Metab Disord. 2010 Sep;11(3):171-8. doi: 10.1007/s11154-010-9146-0.
The hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common form of congenital hyperinsulinism (HI). Children affected by this syndrome have both fasting and protein sensitive hypoglycemia combined with persistently elevated ammonia levels. Gain of function mutations in the mitochondrial enzyme glutamate dehydrogenase (GDH) are responsible for the HI/HA syndrome. GDH is expressed in liver, kidney, brain, and pancreatic beta-cells. Patients with the HI/HA syndrome have an increased frequency of generalized seizures, especially absence-type seizures, in the absence of hypoglycemia. The hypoglycemia of the HI/HA syndrome is well controlled with diazoxide, a KATP channel agonist. GDH has also been implicated in another form of HI, short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency associated HI. The HI/HA syndrome provides a rare example of an inborn error of intermediary metabolism in which the effect of the mutation on enzyme activity is a gain of function.
高胰岛素血症/高血氨（HI/HA）综合征是第二常见的先天性高胰岛素血症（HI）形式。受这种综合征影响的儿童既有空腹低血糖，也有蛋白质敏感型低血糖，同时伴有持续升高的血氨水平。线粒体酶谷氨酸脱氢酶（GDH）的功能获得性突变导致 HI/HA 综合征。GDH 在肝脏、肾脏、大脑和胰腺β细胞中表达。患有 HI/HA 综合征的患者在没有低血糖的情况下，癫痫发作的频率更高，尤其是失神发作。HI/HA 综合征的低血糖可以通过 KATP 通道激动剂二氮嗪得到很好的控制。GDH 还与另一种 HI 形式有关，即短链 3-羟基酰基辅酶 A 脱氢酶（SCHAD）缺乏相关 HI。HI/HA 综合征提供了一个罕见的中间代谢障碍的先天性错误的例子，其中突变对酶活性的影响是功能获得性的。
