title: Functional hyperactivity of hepatic glutamate dehydrogenase as a cause of the hyperinsulinism/hyperammonemia syndrome: effect of treatment.
abstract: OBJECTIVE
  The combination of persistent hyperammonemia and hypoketotic hypoglycemia in infancy presents a diagnostic challenge. Investigation of the possible causes and regulators of the ammonia and glucose disposal may result in a true diagnosis and predict an optimum treatment.
  
  
  METHODS
  Since the neonatal period, a white girl had been treated for hyperammonemia and postprandial hypoglycemia with intermittent hyperinsulinism. Her blood level of ammonia varied from 100 to 300 micromol/L and was independent of the protein intake.
  
  
  METHODS
  Enzymes of the urea cycle as well as glutamine synthetase and glutamate dehydrogenase (GDH) were assayed in liver tissue and/or lymphocytes.
  
  
  RESULTS
  The activity of hepatic GDH was 874 nmol/(min.mg protein) (controls: 472-938). Half-maximum inhibition by guanosine triphosphate was reached at a concentration of 3.9 micromol/L (mean control values:.32). The ratio of plasma glutamine/blood ammonia was unusually low. Oral supplements with N-carbamylglutamate resulted in a moderate decrease of the blood level of ammonia. The hyperinsulinism was successfully treated with diazoxide.
  
  
  CONCLUSIONS
  A continuous conversion of glutamate to 2-oxoglutarate causes a depletion of glutamate needed for the synthesis of N-acetylglutamate, the catalyst of the urea synthesis starting with ammonia. In addition, the shortage of glutamate may lead to an insufficient formation of glutamine by glutamine synthetase. As GDH stimulates the release of insulin, the concomitant hyperinsulinism can be explained. This disorder should be considered in every patient with postprandial hypoglycemia and diet-independent hyperammonemia.
authors.affiliation: Erasmus University, Department of Clinical Genetics, Rotterdam, The Netherlands. huijmans@kgen.fgg.eur.nl
authors.forename: J G
authors.initials: JG
authors.lastname: Huijmans
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: J B
authors.initials: JB
authors.lastname: de Klerk
authors.forename: M J
authors.initials: MJ
authors.lastname: Rovers
authors.forename: H R
authors.initials: HR
authors.lastname: Scholte
mesh_terms: D000641:Ammonia / Q000097:blood*; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007003:Hypoglycemia / Q000201:enzymology; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology*; D019518:Postprandial Period; D013577:Syndrome
chemical_list: D000641:Ammonia; D005969:Glutamate Dehydrogenase