Presentation and management of N -acetylglutamate synthase deficiency: a review of the literature
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Presentation and management of N‑acetylglutamate synthase deficiency: a review of the literature Aileen Kenneson1* and Rani H. Singh1,2*
Abstract 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. Keywords: N-Acetylglutamate synthase, NAGS, N-Acetylglutamate synthase deficiency, Inherited metabolic disorder, Urea cycle, Hyperammonemia, Carbamylglutamate, Carbaglu
*Correspondence: [email protected]; [email protected] 1 Department of Human Genetics, Emory University, Atlanta, GA, USA Full list of author information is available at the end of the article
Background Ammonia is the toxic product of excess nitrogen in the body. Ammonia is detoxified in the liver by conversion to urea via a series of enzymatic reactions in the urea cycle (Fig. 1) [1]. Disorders of the urea cycle result in episodes of hyperammonemia, which can present
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.
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