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01-11-2017 | Review

Liver involvement in urea cycle disorders: a review of the literature

Authors: Adrien Bigot, Michel C. Tchan, Benjamin Thoreau, Hélène Blasco, François Maillot

Published in: Journal of Inherited Metabolic Disease | Issue 6/2017

Abstract

Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology. Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs. Excessive glycogen storage is also a prominent histologic feature, and hypoglycemia has been reported in citrin deficiency. Hepatocarcinomas seem frequent in some UCDs, such as in citrin deficiency, and can sometimes occur in non-cirrhotic patients. UCDs may differ in liver involvement according to the enzymatic deficiency. Ornithine transcarbamylase deficiency may be associated more with acute liver failure and argininosuccinic aciduria with chronic liver failure and cirrhosis. Direct toxicity of metabolites, downstream metabolic deficiencies, impaired tricarboxylic acid cycle, oxidative stress, mitochondrial dysfunction, energy deficit, and putative toxicity of therapies combine in various ways to cause the different liver diseases reported.

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Title: Liver involvement in urea cycle disorders: a review of the literature
Authors: Adrien Bigot
Michel C. Tchan
Benjamin Thoreau
Hélène Blasco
François Maillot
Publication date: 01-11-2017
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 6/2017
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-017-0088-5

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