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NAGS Deficiency

N-acetylglutamate synthetase (NAGS) deficiency is a rare genetic disorder caused by complete or partial absence of the N-acetylglutamate synthetase (NAGS) enzyme that is a crucial component of the urea cycle. The urea cycle is the body’s way of neutralizing highly toxic ammonia, produced from protein breakdown, into the less toxic urea, which can be removed by the urine. The NAGS enzyme, along with an additional enzymes in the urea cycle, carry out sequential steps, similar to people in an assembly line, to remove the toxic ammonia from the body. A deficiency in the NAGS enzyme causes a buildup of ammonia (hyperammonemia) which can lead to serious complications, including permanent neurological damage, coma, or death.

NAGS deficiency is an underdiagnosed disease and the number of individuals affected remains unknown, although it is believed that the 1 in every 35,000 newborns suffers with urea cycle disorder.1 Infants born with complete NAGS deficiency may present with complications within hours to days after birth. However, individuals with partial absence of NAGS may not be diagnosed until much later, usually due to another complication.

Family history, blood tests, liver biopsy, and genetic testing are useful in determining NAGS deficiency in patients experiencing signs of hyperammonemia. In individuals with family history of known or suspected urea cycle disorders, genetic counseling and pregnancy planning is strongly recommended.

Symptoms related to high levels of ammonia in the blood (hyperammonemia) include, but are not limited to:

Newborn Children – initial symptoms

  • Poor feeding
  • Vomiting
  • Abnormal drowsiness
  • Loss of appetite
  • Breathing too fast
  • Muscle weakness
  • Seizures

Any Age (Mild or partial UCD)

  • Loss of appetite
  • Vomiting
  • Abdominal pain
  • Poor growth
  • Failure to gain weight
  • Abnormal behaviors
  • Muscle weakness

Long-term management of NAGS deficiency requires maintaining a low protein diet. Drug therapy for individuals with urea cycle disorder due to NAGS deficiency differs from patients with sufficient amount of NAGS.

Current drug therapy for NAGS deficiency at Accredo includes:

  • Carbaglu – For the treatment of patients with urea cycle disorder due to NAGS deficiency.


  1. Summar ML, Koelker S, and Freedenberg D, et al. European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD). Mol Genet Metab. 2013 Sep-Oct;110(1-2):179-80.

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