A case of hyperinsulinism/hyperammonaemia syndrome: usefulness of the oral protein tolerance for the evaluation of treatment

Excerpt

Hyperinsulinism/hyperammonaemia (HI/HA) syndrome (OMIM 606762) was first reported by Zammarchi et al. [7] and Weinzimer et al. [6] in the late 1990 s as cases of hyperinsulinism with hypoglycaemia having persistently high plasma ammonium levels. In 1998, Stanley et al. [4] reported that HI/HA syndrome is caused by mutations in the glutamate dehydrogenase (GDH) gene [4]. It is known that the occurrence of HI/HA is as follows [3]. As the result of the overactivity of GDH, a mitochondrial matrix enzyme, there is an increase in the ATP/ADP ratio and a reduction in glutamate using NAD or NADP as a coenzyme. Leucine acts as an activator of GDH resulting in hyperinsulinism. Hyperammonaemia results from the decrease in glutamate which in turn decreases the level of N-acetylglutamate, an activator of carbamoyl-phosphate synthetase, the first step in ammonia metabolism. HI/HA syndrome is considered to be an autosomal dominant inherited disorder, although a de novo mutation is often observed. Administration of diazoxide, which inhibits insulin secretion, is considered to be an effective treatment for HI/HA syndrome [2,5]. The present study reports our experience of a case of HI/HA syndrome in which the oral protein tolerance test was useful in evaluation of treatment. …