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. PATIENT:
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.
CONCLUSION: 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
