Late-onset n-acetylglutamate synthase deficiency: Report of a paradigmatic adult case presenting with headaches and review of the literature

Catia Cavicchi, Chiara Chilleri, Antonella Fioravanti, Lorenzo Ferri, Francesco Ripandelli, Cinzia Costa, Paolo Calabresi, Paolo Prontera, Francesca Pochiero, Elisabetta Pasquini, Silvia Funghini, Giancarlo La Marca, Maria Alice Donati, Amelia Morrone

Risultato della ricerca: Contributo in rivistaArticolo in rivista

3 Citazioni (Scopus)


N-acetylglutamate synthase deficiency (NAGSD) is an extremely rare urea cycle disorder (UCD) with few adult cases so far described. Diagnosis of late-onset presentations is difficult and delayed treatment may increase the risk of severe hyperammonemia. We describe a 52-year-old woman with recurrent headaches who experienced an acute onset of NAGSD. As very few papers focus on headaches in UCDs, we also report a literature review of types and pathophysiologic mechanisms of UCD-related headaches. In our case, headaches had been present since puberty (3-4 days a week) and were often accompanied by nausea, vomiting, or behavioural changes. Despite three previous episodes of altered consciousness, ammonia was measured for the first time at 52 years and levels were increased. Identification of the new homozygous c.344C>T (p.Ala115Val) NAGS variant allowed the definite diagnosis of NAGSD. Bioinformatic analysis suggested that an order/disorder alteration of the mutated form could affect the arginine-binding site, resulting in poor enzyme activation and late-onset presentation. After optimized treatment for NAGSD, ammonia and amino acid levels were constantly normal and prevented other headache bouts. The manuscript underlies that headache may be the presenting symptom of UCDs and provides clues for the rapid diagnosis and treatment of late-onset NAGSD.
Lingua originaleEnglish
pagine (da-a)1-9
Numero di pagine9
RivistaInternational Journal of Molecular Sciences
Stato di pubblicazionePubblicato - 2018


  • Age of Onset
  • Amino-Acid N-Acetyltransferase
  • Biomarkers
  • Brain
  • Electroencephalography
  • Female
  • Glutamates
  • Headaches
  • Humans
  • Hyperammonemic encephalopathy
  • Late-onset UCDs
  • Middle Aged
  • N-acetylglutamate synthase deficiency (NAGSD)
  • N-carbamylglutamate (NCG)
  • NAGS gene mutations
  • Symptom Assessment
  • Treatment Outcome
  • Urea Cycle Disorders, Inborn
  • Urea cycle disorders (UCDs)


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