Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency

  • Anne-Els van de Logt
  • Leo A. J. Kluijtmans
  • Marleen C. D. G. Huigen
  • Mirian C. H. JanssenEmail author
Case Report
Part of the JIMD Reports book series (JIMD, volume 31)


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 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 μM.

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.


Intellectual Disability Ammonia Level Urea Cycle Sodium Benzoate Orotic Acid 
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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Anne-Els van de Logt
    • 1
  • Leo A. J. Kluijtmans
    • 2
  • Marleen C. D. G. Huigen
    • 2
  • Mirian C. H. Janssen
    • 1
    Email author
  1. 1.Department of Internal MedicineRadboud University Medical CenterNijmegenThe Netherlands
  2. 2.Department of Laboratory Medicine, Translational Metabolic Laboratory (TML)Radboud University Medical CenterNijmegenThe Netherlands

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