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Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature
BACKGROUND: N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated wi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545900/ https://www.ncbi.nlm.nih.gov/pubmed/33036647 http://dx.doi.org/10.1186/s13023-020-01560-z |
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author | Kenneson, Aileen Singh, Rani H. |
author_facet | Kenneson, Aileen Singh, Rani H. |
author_sort | Kenneson, Aileen |
collection | PubMed |
description | BACKGROUND: N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management. METHODS: Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers. RESULTS: In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported. CONCLUSIONS: Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate. |
format | Online Article Text |
id | pubmed-7545900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75459002020-10-13 Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature Kenneson, Aileen Singh, Rani H. Orphanet J Rare Dis Review BACKGROUND: N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management. METHODS: Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers. RESULTS: In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported. CONCLUSIONS: Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate. BioMed Central 2020-10-09 /pmc/articles/PMC7545900/ /pubmed/33036647 http://dx.doi.org/10.1186/s13023-020-01560-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Kenneson, Aileen Singh, Rani H. Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature |
title | Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature |
title_full | Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature |
title_fullStr | Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature |
title_full_unstemmed | Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature |
title_short | Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature |
title_sort | presentation and management of n-acetylglutamate synthase deficiency: a review of the literature |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545900/ https://www.ncbi.nlm.nih.gov/pubmed/33036647 http://dx.doi.org/10.1186/s13023-020-01560-z |
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