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Clinical practice

The management of hyperammonemia

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Abstract

Hyperammonemia is a life-threatening condition which can affect patients at any age. Elevations of ammonia in plasma indicate its increased production and/or decreased detoxification. The hepatic urea cycle is the main pathway to detoxify ammonia; it can be defective due to an inherited enzyme deficiency or secondary to accumulated toxic metabolites or substrate depletion. Clinical signs and symptoms in hyperammonemia are unspecific but they are mostly neurological. Thus, in any unexplained change in consciousness or in any unexplained encephalopathy, hyperammonemia must be excluded as fast as possible. Any delay in recognition and start of treatment of hyperammonemia may have deleterious consequences for the patient. Treatment largely depends on the underlying cause but is, at least in pediatric patients, mainly aimed at establishing anabolism to avoid endogenous protein breakdown and amino acid imbalances. In addition, pharmacological treatment options exist to improve urea cycle function or to remove nitrogen, but their use depend on the underlying disorder. To improve the prognosis of acute hyperammonemia, an increased awareness of this condition is probably more needed than anything else. Likewise, the immediate start of appropriate therapy is of utmost importance. This review focuses on a better understanding of factors leading to ammonia elevations and on practical aspects related to diagnosis and treatment in order to improve clinical management of hyperammonemia.

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Acknowledgement

The author acknowledges the contribution of the reviewers of this manuscript and in particular the help of Claude Bachmann during revision of this review.

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The author has no financial conflicts of interest to report.

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  1. Kinderspital Zurich, Division of Metabolism, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Johannes Häberle

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  1. Johannes Häberle
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Correspondence to Johannes Häberle.

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Additional note

The author is currently steering an international working group (including Nathalie Boddaert, Paris; Alberto Burlina, Padua; Anupam Chakrapani, Birmingham; Carlo Dionisi-Vici, Rome; Marjorie Dixon, London; Martina Huemer, Bregenz; Daniela Karall, Innsbruck; Martin Lindner, Heidelberg; Vicente Rubio, Valencia; Aude Servais, Paris; Pablo Sanjurjo, Bilbao; René Santer, Hamburg; Vassili Valayannopoulos, Paris) on “Guidelines for the diagnosis and treatment of urea cycle disorders”. The author is much obliged to all members of the working group who helped to evaluate the literature and actively discussed many issues closely related to hyperammonemia. The Guideline will be released to many European National Metabolic Societies and as a publication in 2011 and might provide additional information for the reader interested in management of hyperammonemia.

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Häberle, J. Clinical practice. Eur J Pediatr 170, 21–34 (2011). https://doi.org/10.1007/s00431-010-1369-2

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