(acronym for N-Acetyl Glutamate Synthetase)

[MIM 237 310]

Prevalence: 1/70,000. Autosomal recessive transmission of a mutation of the NAGS gene (17q21.31). Deficiency in N-acetyl glutamate synthase, mitochondrial enzyme that activates the first step in the urea cycle. 

Clinical signs vary depending on the age of onset of symptoms and the importance of deficiency:

-         neonatal period: hyperammonemia with vomiting, lethargy or irritability;

-         infant: anorexia, vomiting, development retardation, hepatomegaly. A digestive cause to these problems is often searched for before the diagnosis is established;

-         childhood and adolescence: clinical picture of acute encephalopathy in the context  of a stress (fever, protein, postoperative catabolism) or progressive neurological symptomatology (mental retardation, seizures, ataxia).

The diagnosis is sometimes made at the time of a brisk decompensation during an infectious episode (pseudo Reye's syndrome). Treatment: daily oral administration of N-carbamyl glutamic (30-250 mg/kg/day) according to blood levels of NH4 and urea. A protein poor diet is not necessary.

Anesthetic implications: see Urea cycle disorders

the duration of preoperative fasting should be as short as possible: administer a electrolytic glucose solution as soon as the fasting period begins. Empty the stomach to prevent any protein intake in case of digestive surgery where blood may be swallowed (ENT, stomatology). Special monitoring: NH4 (nl < 50 µmol/L), blood glucose. Provide anesthesia deep enough to  decrease the stress response: locoregional anesthesia, morphine, effective postoperative analgesia.

References :  

• Van Leynseele A, Jansen A, Goyens P, Martens G, Peeters S, Jonckheere A, De Meirleir L.
  Early treatment of a child with NAGS deficiency using N-carbamyl glutamate results in a normal neurological outcome.
  Eur J Pediatr 2004; 173: 1635-8. 
• Del Rio C, Martin-Hernandez E, Ruiz A, Quijada-Fraille P, Rubio P.
  Perioperative management of children with urea cycle disorders.
  Pediatr Anesth 2020; 30:780-91.

Updated: August 2021