Hepatic Glutamine Synthetase Deficiency in Fatal Hyperammonemia after Lung Transplantation

15 September 1997 | Volume 127 Issue 6 | Pages 446-449

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.

Author and Article Information

From the University of Minnesota, Minneapolis, Minnesota; and the Hospital of the University of Pennsylvania, The Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Grant Support: In part by public health service grants 1PO1HD32652 from the National Institute of Child Health and Human Development and R01-DK47870 from the National Institute of Diabetes and Digestive and Kidney Diseases.
Requests for Reprints: Mendel Tuchman, MD, Box 400, Mayo Building, University of Minnesota Hospitals, Minneapolis, MN 55455.
Current Author Addresses: Drs. Tuchman and Rajagopal and Mr. McCann: Department of Pediatrics, University of Minnesota Hospitals, 516 Delaware Street South East, Minneapolis, MN 55455.