Case Report

Postchemotherapy Hyperammonemic Encephalopathy Emulating Ornithine Transcarbamoylase (OTC) Deficiency

Authors: Joseph S. Chan, MD, Cary O. Harding, MD, Charles D. Blanke, MD

Abstract

A young patient with hepatocellular carcinoma receiving chemotherapy presented with encephalopathy. Evaluation of the patient revealed a metabolic profile consistent with ornithine transcarbamoylase (OTC) deficiency, an inherited disorder of the urea cycle. The evaluation yielded a plasma amino acid analysis consistent with OTC deficiency. However, genetic analysis did not reveal a somatic mutation of the OTC gene in this patient. The hyperammonemic encephalopathy was reversed by the infusion of arginine, a common treatment for hereditary OTC deficiency. This case may represent a distinct syndrome of reversible hyperammonemia in patients with hepatocellular carcinoma.


Key Points


* This case may represent a distinct syndrome of hyperammonemia in a patient with hepatocellular carcinoma receiving chemotherapy.


* The metabolic profile is consistent with ornithine transcarbamoylase deficiency, but no somatic mutation was detected in the patient.


* The patient’s hyperammonemic encephalopathy was reversed by arginine treatment.


* Patients with encephalopathy and hepatocellular carcinoma should be carefully evaluated for treatable hyperammonemia.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med 1997;337:473–479.
 
2. Mitchell RB, Wagner JE, Karp JE, et al. Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases. Am J Med 1988;85:662–667.
 
3. Yeo W, Mok TS, Zee B, et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst 2005;97:1532–1538.
 
4. Goodman SI, Frerman FE. The Metabolic and Molecular Bases of Inherited Disease 2000, ed 7 New York, McGraw-Hill.
 
5. Lee JC, Chen MJ, Chang CH, et al. Plasma amino acid levels in patients with colorectal cancers and liver cirrhosis with hepatocellular carcinoma. Hepatogastroenterology 2003;50:1269–1273.
 
6. Kim YA, Chung HC, Choi HJ, et al. Intermediate dose 5-fluorouracil-induced encephalopathy. Jpn J Clin Oncol 2006;36:55–59.
 
7. Lukaschek J, Nufer M, Maurer D, et al. Cardiotoxicity and neurotoxicity of high-dose continuous fluorouracil as a result of degradation compounds in the drug vials. J Clin Oncol 2004;22:5022–5025.
 
8. Yeh KH, Cheng AL. High-dose 5-fluorouracil infusional therapy is associated with hyperammonaemia, lactic acidosis and encephalopathy. Br J Cancer 1997;75:464–465.
 
9. Yamaguchi S, Brailey LL, Morizono H, et al. Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum Mutat 2006;27:626–632.
 
10. Winter SS, Rose E, Katz R. Hyperammonemia after chemotherapy in an adolescent with hepatocellular carcinoma. J Pediatr Gastroenterol Nutr 1997;25:537–540.
 
11. Jeffers LJ, Dubow RA, Zieve L, et al. Hepatic encephalopathy and orotic aciduria associated with hepatocellular carcinoma in a noncirrhotic liver. Hepatology 1988;8:78–81.
 
12. Bresnick E, Mayfield ED Jr, Liebelt AG, et al. Enzyme patterns in a group of transplantable mouse hepatomas of different growth rates. Cancer Res 1971;31:743–751.
 
13. Weber G, Queener SF, Morris HP. Imbalance in ornithine metabolism in hepatomas of different growth rates as expressed in behavior of l-ornithine carbamyl transferase activity. Cancer Res 1972;32:1933–1940.