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The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders

  • Original Article
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Journal of Inherited Metabolic Disease

Abstract

Neonatal onset hyperammonemia in patients with urea cycle disorders (UCDs) is still associated with high morbidity and mortality. Current protocols consistently recommend emergency medical and dietary management. In case of increasing or persistent hyperammonemia, with continuous or progressive neurological signs, dialysis is performed, mostly as ultima ratio. It is presently unknown whether the currently defined ammonia threshold (e.g., at 500 μmol/L) to start dialysis is useful to improve clinical outcome. A systematic review of clinical and biochemical data from published neonatal onset UCD patients was performed to identify factors determining clinical outcome and to investigate in which clinical and biochemical setting dialysis was most effective. A total of 202 patients (118 proximal and 84 distal UCDs) described in 90 case reports or case series were included according to predefined inclusion/exclusion criteria. Median age at onset was three days and mean ammonia that triggered start of dialysis was 1199 μmol/L. Seventy-one percent of all patients received any form of dialysis. Total mortality was 25% and only 20% of all patients had a “normal” outcome. In general, patients with higher ammonia levels were more likely to receive dialysis, but this had for most patients no influence on outcome. In conclusion, in severe neonatal onset hyperammonemia, the current practice of dialysis, which effectively clears ammonia, had no impact on outcome. It may be essential for improving outcome to initiate all available treatment options, including dialysis, as early as possible.

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Acknowledgements

This study was supported by the Swiss National Science Foundation (grant 310030_153196). The authors are grateful to Jin-Ho Choi & Han-Wook Yoo, MD, PhD, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, who helped to complete missing data.

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  1. Martina Huemer and Johannes Häberle contributed equally to this work.

Authors and Affiliations

  1. Division of Metabolism and Children’s Research Center, University Children’s Hospital Zurich, 8032, Zurich, Switzerland

    Nina Hediger, Carmen Diez-Fernandez, Martina Huemer & Johannes Häberle

  2. Department of Psychosomatics and Psychiatry, University Children’s Hospital Zurich, 8032, Zurich, Switzerland

    Markus A. Landolt

  3. Division of Child and Adolescent Health Psychology, Department of Psychology, University of Zurich, Zurich, Switzerland

    Markus A. Landolt

  4. Department of Paediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria

    Martina Huemer

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  1. Nina Hediger
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Correspondence to Johannes Häberle.

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Hediger, N., Landolt, M.A., Diez-Fernandez, C. et al. The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders. J Inherit Metab Dis 41, 689–698 (2018). https://doi.org/10.1007/s10545-018-0157-4

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