Dataset Information

Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency.

ABSTRACT: A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 ?M. Acquired disorders as explanation for the hyperammonemia were excluded. Metabolic investigations showed an elevated glutamine and alanine and low citrulline, suspect for a urea cycle defect (UCD). Orotic acid could not be demonstrated in urine. DNA investigations were negative for mutations or deletions in the OTC and CPS1 gene, but revealed a homozygous c.603G>C mutation in exon 2 of the N-acetylglutamate synthase (NAGS) gene (NM_153006.2:c.603G>C), which mandates p.Lys201Asn. This is a novel mutation in the NAGS gene.After the diagnosis of NAGS deficiency was made carbamylglutamate was started in a low dose. In combination with mild protein restriction the ammonia level decreased to 26 ?M.This is one of the first patients in literature in whom the diagnosis of a UCD is made at such an advanced age. It is important for the adult physician to consider a metabolic disorder at every age.

SUBMITTER: van de Logt AE

PROVIDER: S-EPMC5272844 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency.

van de Logt Anne-Els AE Kluijtmans Leo A J LA Huigen Marleen C D G MC Janssen Mirian C H MC

JIMD reports 20160505

A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 μM. Acquired disorders as explanation for the hyperammonemia were excluded. Metabolic investigations showed an elevated glutamine and alanine and low citrulline, suspect for a urea cycle defect (UCD). Orotic acid could not be demonstrated in urine. DNA investigations were n ...[more]

PMID: 27147233

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Project 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.

Dataset Information

Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency.

Publications

Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency.

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