Hyperinsulinism-hyperammonemia syndrome. Glutamate dehydrogenase deficiency.
Incidence
Autosomal dominant
Clinical Characteristics
A distinct syndrome of hyperinsulinism and hyperammonemia in 3 unrelated children was described by Zammarchi et al. (1996) and Weinzimer et al. (1997). In addition, Zammarchi et al. (1996) suggested that the defect involved leucine hypersensitivity. Stanley et al. (1997) identified 6 unrelated infants with hypoglycemia due to congenital hyperinsulinism combined with persistent unexplained hyperammonemia. In each of these cases, known metabolic disorders were ruled out. Hsu et al. (2001) studied 8 children and 6 adults with hyperinsulinism/hyperammonemia syndrome. All had dominantly expressed mutations of glutamine dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with hyperinsulinism/hyperammonemia showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with hyperinsulinism/hyperammonemia and control subjects. Hsu et al. (2001) concluded that the postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the hyperinsulinism/hyperammonemia syndrome.
Precipitants
The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the hyperinsulinism/hyperammonemia syndrome. Fasting also may trigger an attack of hypoglycemia.
Provocation Tests
The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the hyperinsulinism/hyperammonemia syndrome. There is inappropriate glycemic responses to glucagon that are characteristic of hyperinsulinism.
Diagnostic Procedures
Laboratory testing. Caused by mutations in the glutamate dehydrogenase gene (GLUD1). There is inappropriate glycemic responses to glucagon that are characteristic of hyperinsulinism.