Reviews in Endocrine and Metabolic Disorders

, Volume 11, Issue 3, pp 171–178

The hyperinsulinism/hyperammonemia syndrome

Article

Abstract

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.

Keywords

Hyperinsulinism Hyperammonemia Glutamate dehydrogenase Hypoglycemia short-chain 3-hydroxyacyl-CoA dehydrogenase 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.The Children’s Hospital of Philadelphia, Division of Endocrinology and DiabetesUniversity of Pennsylvania, School of MedicinePhiladelphiaUSA

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