N-acetylglutamate synthase deficiency with associated 3-methylglutaconic aciduria: A case report.

Autor: Selvanathan A; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Demetriou K; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Lynch M; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Lipke M; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Bursle C; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Elliott A; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Inwood A; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia., Foyn L; Chemical Pathology, Central Laboratory Pathology Queensland Herston Australia., McWhinney B; Chemical Pathology, Central Laboratory Pathology Queensland Herston Australia., Coman D; Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane Australia.; School of Medicine University of Queensland Brisbane Australia., McGill J; Chemical Pathology, Central Laboratory Pathology Queensland Herston Australia.
Jazyk: angličtina
Zdroj: JIMD reports [JIMD Rep] 2022 Jul 22; Vol. 63 (5), pp. 420-424. Date of Electronic Publication: 2022 Jul 22 (Print Publication: 2022).
DOI: 10.1002/jmd2.12318
Abstrakt: N-acetylglutamate synthase (NAGS) deficiency is a rare autosomal recessive disorder, which results in the inability to activate the key urea cycle enzyme, carbamoylphosphate synthetase 1 (CPS1). Patients often suffer life-threatening episodes of hyperammonaemia, both in the neonatal period and also at subsequent times of catabolic stress. Because NAGS generates the cofactor for CPS1, these two disorders are difficult to distinguish biochemically. However, there have now been numerous case reports of 3-methylglutaconic aciduria (3-MGA), a marker seen in mitochondrial disorders, occurring in CPS1 deficiency. Previously, this had not been reported in NAGS deficiency. We report a four-day-old neonate who was noted to have 3-MGA at the time of significant hyperammonaemia and lactic acidosis. Low plasma citrulline and borderline orotic aciduria were additional findings that suggested a proximal urea cycle disorder. Subsequent molecular testing identified bi-allelic pathogenic variants in NAGS . The 3-MGA was present at the time of persistent lactic acidosis, but improved with normalization of serum lactate, suggesting that it may reflect secondary mitochondrial dysfunction. NAGS deficiency should therefore also be considered in patients with hyperammonaemia and 3-MGA. Studies in larger numbers of patients are required to determine whether it could be a biomarker for severe decompensations.
Competing Interests: We declare no conflicts of interest.
(© 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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