Background: The cause of severe acquired hyperammonemia, an uncommon but often fatal complication of organ transplantation and chemotherapy for cancer, is obscure.
Objective: To test the hypothesis that liver glutamine synthetase deficiency may explain hyperammonemia in patients who have had organ transplantation or are receiving chemotherapy.
Design: Case report.
Patients: Two patients who had fatal hyperammonemia after orthotopic lung transplantation.
Measurements: Liver tissue was analyzed to determine the activities of two urea cycle enzymes and glutamine synthetase. Western blot assays for hepatic glutamine synthetase were performed to determine whether glutamine synthetase deficiency resulted from reduced enzyme levels.
Results: Activities of carbamoyl phosphate synthetase I and ornithine carbamoyltransferase in the liver were normal. The activity of hepatic glutamine synthetase was markedly reduced (in patient 1, 12% of the mean value in controls; in patient 2, 28% of the mean value in controls), and a concomitant reduction in the amount of glutamine synthetase protein was observed.
Conclusion: Hyperammonemia after transplantation was associated with hepatic glutamine synthetase deficiency in two patients, but the causal relation between these two conditions must be further studied.