Correspondence

Death after Transplantation of a Liver from a Donor with Unrecognized Ornithine Transcarbamylase Deficiency

N Engl J Med 1999; 341:921-922September 16, 1999

Article

To the Editor:

Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle.1,2 It is an X-linked disease that can range in severity from hyperammonemic coma in neonates to the absence of symptoms in adults.1,2 Liver transplantation is an effective treatment for patients with this disease.3 However, this disease has another implication for liver transplantation, as demonstrated by the following case.

In December 1998, a 65-year-old woman underwent orthotopic liver transplantation for liver cirrhosis related to hepatitis C infection and hepatocellular carcinoma. She was extubated on the first postoperative day and initially did well (Table 1Table 1Clinical Course of the Liver-Transplant Recipient and Associated Laboratory Values.). However, on the third day after surgery, she had nausea and became somnolent. Initially, a computed tomographic (CT) scan of the brain was normal. Twenty-four hours later, a CT scan showed severe cerebral edema. Laboratory investigations showed extremely high blood levels of ammonia (Table 1). All other laboratory values and the results of diagnostic tests for hepatic perfusion (Doppler ultrasonography and clearance of indocyanine green4) were normal or within the range expected after liver transplantation. The blood level of ammonia was reduced by continuous hemofiltration. However, multiorgan failure developed, and the patient died six days after the surgery.

The isolated finding of high ammonia levels suggested a disorder of the urea cycle. We hypothesized that a liver deficient in ornithine transcarbamylase had been transplanted. Subsequently, the diagnosis of ornithine transcarbamylase deficiency was established by enzyme analysis of a biopsy specimen of the transplanted liver.1 The activity of ornithine transcarbamylase measured in the liver tissue was approximately 10 percent of normal, whereas the activity of other enzymes of the urea cycle was normal. Molecular analysis revealed a point mutation at codon 40 of exon 2 of the ornithine transcarbamylase gene (CGT to CAT, resulting in a change from arginine to histidine), which is associated with late-onset symptoms in males.1 This finding established that an ornithine transcarbamylase–deficient liver had been transplanted. Further evaluation of the donor's history lent support to the diagnosis. He was a 26-year-old man who had died of brain edema of unknown origin. A maternal uncle of the donor had also died from coma of unknown origin.

Although rare, transplantation of a liver from a donor with unrecognized ornithine transcarbamylase deficiency is a potential hazard to the recipient and may lead to the recipient's death.

Walter Plöchl, M.D.
Christian K. Spiss, M.D.
University of Vienna, A-1090 Vienna, Austria

Engelbert Plöchl, M.D.
St. Johann's Hospital, A-5020 Salzburg, Austria

4 References

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Citing Articles (9)

Citing Articles

1. 1

   Alexander Belenky, Igor Igov, Youval Konstantino, Gil N. Bachar, Eitan Mor, Franklyn Graif, Ziv Ben-Ari, Ran Tur-Kaspa, Eli Atar. (2009) Endovascular Diagnosis and Intervention in Patients with Isolated Hyperammonemia, with or without Ascites, after Liver Transplantation. Journal of Vascular and Interventional Radiology 20:2, 259-263
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   Sanae Numata, Eimei Harada, Yasuki Maeno, Isao Ueki, Yoriko Watanabe, Chieko Fujii, Takashi Yanagawa, Satoshi Takenaka, Toshiro Inoue, Shinkai Inoue, Terufumi Goushi, Tsutomu Yasutake, Toshihiko Mizuta, Makoto Yoshino. (2008) Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients. Journal of Human Genetics 53:1, 10-17
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   Daisuke Morioka, Mureo Kasahara, Yasutsugu Takada, Jose Pablo Garbanzo Corrales, Atsushi Yoshizawa, Seisuke Sakamoto, Kaoru Taira, Elena Yukie Yoshitoshi, Hiroto Egawa, Hiroshi Shimada, Koichi Tanaka. (2005) Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders. American Journal of Transplantation 5:11, 2754-2763
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   Daisuke Morioka, Mureo Kasahara, Yasutsugu Takada, Yasumasa Shirouzu, Kaoru Taira, Seisuke Sakamoto, Kenji Uryuhara, Hiroto Egawa, Hiroshi Shimada, Koichi Tanaka. (2005) Current role of liver transplantation for the treatment of urea cycle disorders: A review of the worldwide English literature and 13 cases at Kyoto University. Liver Transplantation 11:11, 1332-1342
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5. 5

   Daisuke Morioka, Yasutsugu Takada, Mureo Kasahara, Takashi Ito, Kenji Uryuhara, Kohei Ogawa, Hiroto Egawa, Koichi Tanaka. (2005) Living Donor Liver Transplantation for Noncirrhotic Inheritable Metabolic Liver Diseases: Impact of the Use of Heterozygous Donors. Transplantation 80:5, 623-628
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   Suzanne V. Mcdiarmid. 2005. Liver Transplantation for Metabolic Disease. , 337-366.
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   Neil Gordon. (2003) Ornithine transcarbamylase deficiency: a urea cycle defect. European Journal of Paediatric Neurology 7:3, 115-121
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8. 8

   W. Plochl, S. Kozek-Langenecker, C.K. Spiss, E. Plochl, H. Pokorny, J. Zacherl, F. Muhlbacher, S. Stockler-Ipsiroglu, B. Wermuth. (2001) Multiorgan donation from a donor with unrecognized ornithine transcarbamylase deficiency. Transplant International 14:3, 196-201
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   E Ploechl, W Ploechl, S Stoeckler-Ipsiroglu, H Pokorny, B Wermuth. (2001) Late-onset ornithine transcarbamylase deficiency in two families with different mutations in the same codon. Clinical Genetics 59:2, 111-114
   CrossRef