What are the other Names for this Condition? (Also known as/Synonyms)

• Hyperammonemia due to N-Acetylglutamate Synthetase Deficiency
• N-Acetyl Glutamate Synthetase Deficiency Disorder
• NAGS Deficiency Disorder

What is N-Acetylglutamate Synthetase Deficiency Disorder? (Definition/Background Information)

• N-Acetylglutamate Synthase Deficiency (NAGS) Disorder is type of metabolic disorder that affects the processing of proteins and removal of ammonia from the body
• When proteins are processed by the body, ammonia is formed. Individuals with NAGS are not able to remove ammonia from the body and have symptoms due to toxic levels of ammonia that build up in the blood
• NAGS Deficiency Disorder and other similar disorders are a type of metabolic condition known as a urea cycle disorder
• Signs and symptoms in newborns with N-Acetylglutamate Synthase Deficiency Disorder may include a lack of energy, unwillingness to eat, seizures, unusual body movements, and poorly controlled breathing or body temperature
• Complications may include coma, developmental delay, and learning disability. Some people have a less severe form of the deficiency with earliest symptoms manifesting later in life, particularly following high-protein meals, illness, or other stress
• Signs and symptoms of N-Acetylglutamate Synthase Deficiency Disorder may include sudden vomiting, lack of coordination, confusion, and coma
• N-Acetylglutamate Synthase Deficiency Disorder is caused by mutations in the NAGS gene and is inherited in an autosomal recessive fashion
• The treatment of N-Acetylglutamate Synthase Deficiency Disorder may include maintaining a low protein diet and using medications that provide alternative routes to remove ammonia from the body

(Source: N-Acetylglutamate Synthetase Deficiency; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets N-Acetylglutamate Synthetase Deficiency Disorder? (Age and Sex Distribution)

• N-Acetylglutamate Synthase Deficiency Disorder is a rare congenital disorder. Its exact prevalence is not known
• The onset of symptoms may occur at any age
• Both males and females may be affected
• The age of onset is in childhood either in the neonatal period or infancy

What are the Risk Factors for N-Acetylglutamate Synthetase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since N-Acetylglutamate Synthase Deficiency Disorder is an inherited condition
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of N-Acetylglutamate Synthetase Deficiency Disorder? (Etiology)

• N-Acetylglutamate Synthase Deficiency Disorder is caused by mutation(s) in the NAGS gene, which codes for the enzyme N-acetylglutamate synthase
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of N-Acetylglutamate Synthetase Deficiency Disorder?

The signs and symptoms of N-Acetylglutamate Synthetase Deficiency Disorder may include:

• Aggressive behavior
• Cognitive impairment
• Confusion
• Failure to thrive
• Hyperammonemia
• Lethargy 
• Respiratory distress
• Seizures
• Vomiting

(Source: N-Acetylglutamate Synthetase Deficiency; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is N-Acetylglutamate Synthetase Deficiency Disorder Diagnosed?

N-Acetylglutamate Synthetase Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests, including tests for checking activity of NAGS enzyme in the liver
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of N-Acetylglutamate Synthetase Deficiency Disorder?

The complications of N-Acetylglutamate Synthetase Deficiency Disorder may include:

• Severe malnutrition
• Risks of falls and injury if seizures are present
• Hyperammonemic coma

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is N-Acetylglutamate Synthetase Deficiency Disorder Treated?

There is no cure for N-Acetylglutamate Synthetase Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The methods of treatment may include:

• Adhering to a low protein diet
• A daily administration of N-carbamyl-L-glutamate (NCLG), a structural analogue of N-acetylglutamate

How can N-Acetylglutamate Synthetase Deficiency Disorder be Prevented?

Currently, N-Acetylglutamate Synthetase Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of N-Acetylglutamate Synthetase Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of N-Acetylglutamate Synthetase Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• With a timely diagnosis and treatment with NCLG, most affected individuals find relief from symptoms, with a resultant good quality of life
• Without treatment however, the condition could worsen in due course and may be fatal
• The prognosis of NAG Synthetase Deficiency Disorder may be assessed on a case-by-case basis

Additional and Relevant Useful Information for N-Acetylglutamate Synthetase Deficiency Disorder:

• N-Acetylglutamate Synthase Deficiency Disorder may also be known as NAG Synthetase Deficiency Disorder

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/