National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

N-acetylglutamate synthase deficiency


Other Names:
Hyperammonemia due to N-Acetylglutamate Synthetase Deficiency; NAGS deficiency; NAG synthetase deficiency; Hyperammonemia due to N-Acetylglutamate Synthetase Deficiency; NAGS deficiency; NAG synthetase deficiency; N-acetyl glutamate synthetase deficiency See More
Categories:
This disease is grouped under:
N-acetylglutamate synthase deficiency (NAGS) 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 and other similar disorders are a type of metabolic condition known as a urea cycle disorder.[1][2] 

Signs and symptoms in newborns with NAGS 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 may include sudden vomiting, lack of coordination, confusion, and coma. NAGS is caused by mutations in the NAGS gene and is inherited in an autosomal recessive fashion. Treatment may include maintaining a low protein diet and using medications that provide alternative routes to remove ammonia from the body.[1][3]
Last updated: 4/12/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 44 |
Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Nausea 0002018
Vomiting
Throwing up
0002013
5%-29% of people have these symptoms
Acute hyperammonemia 0008281
Agitation 0000713
Anxiety
Excessive, persistent worry and fear
0000739
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Coma 0001259
Drowsiness
Sleepy
0002329
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Fatigue
Tired
Tiredness
[ more ] 		0012378
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Global developmental delay 0001263
Headache
Headaches
0002315
Hyperalaninemia
Increased blood alanine
Increased serum alanine
[ more ] 		0003348
Hyperglutaminemia
High plasma glutamine
0003217
Insomnia
Difficulty staying or falling asleep
0100785
Lethargy 0001254
Loss of consciousness
Passing out
0007185
Mood changes
Moody
0001575
Poor appetite
Decreased appetite
0004396
Poor speech 0002465
Seizure 0001250
1%-4% of people have these symptoms
Ataxia 0001251
Cerebral ischemia
Disruption of blood oxygen supply to brain
0002637
Delirium 0031258
Diarrhea
Watery stool
0002014
Echolalia
Echoing another person's speech
0010529
Encephalopathy 0001298
Hepatomegaly
Enlarged liver
0002240
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Myelodysplasia 0002863
Paraplegia
Leg paralysis
0010550
Polyneuropathy
Peripheral nerve disease
0001271
Psychotic episodes 0000725
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
Reye syndrome-like episodes 0006582
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior
[ more ] 		0000733
Stroke 0001297
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Autosomal recessive inheritance 0000007
Confusion
Disorientation
Easily confused
Mental disorientation
[ more ] 		0001289
Hyperammonemia
High blood ammonia levels
0001987
Increased level of L-glutamic acid in blood 0410068
Showing of 44 |
Last updated: 7/1/2020
NAGS is caused by mutations in the NAGS gene and is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% chance to be affected
  • 50% chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not a carrier
Last updated: 4/12/2017

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • GeneReviews provides a current, expert-authored, peer-reviewed, full-text article urea cycle disorders in general that you may find helpful. GeneReview articles describe the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The NORD Physician Guide for N-acetylglutamate synthase deficiency was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors.  The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition. 
  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.  

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Carglumic acid (Brand name: Carbaglu) - Manufactured by Orphan Europe SARL
    FDA-approved indication: As an adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS) and as manitenance therapy for chronic hyperammonemia due to NAGS deficiency.
    National Library of Medicine Drug Information Portal

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The principle differential diagnosis is carbamoylphosphate synthetase deficiency (see this term).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 
  • The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Patient Registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • Good Days provides help to patients with life-altering conditions. Assistance includes help with the cost of medications and travel.
  • The HealthWell Foundation provides financial assistance for underinsured patients living with chronic and life-altering conditions. They offer help with drug copayments, deductibles, and health insurance premiums for patients with specific diseases. The disease fund status can change over time, so you may need to check back if funds are not currently available.

Education Resources

  • The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on N-acetylglutamate synthase deficiency. This website is maintained by the National Library of Medicine.
  • MedlinePlus.gov provides more information on urea cycle disorders in general. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • The National Urea Cycle Disorders Foundation, a nonprofit organization that supports urea cycle disorders, offers information on urea cycle disorders, including N-acetylglutamate synthase deficiency

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss N-acetylglutamate synthase deficiency. Click on the link to view a sample search on this topic.

News

Other Conferences

  • Reaching for a Cure: 2011 NUCDF Annual Conference, July 8 2011 - July 10, 2011 
    Location: Sheraton Denver Downtown, Denver, Colorado
    Description: This conference offers the unique opportunity to meet other UCD families, stay informed, and learn about new advances in research, treatment and management to improve the lives of children and adults with UCD. Working together, our NUCDF families and community of committed researchers and medical professionals are making a major impact with advances in the understanding of UCDs, accelerating research, and improved outcomes in children and adults with UCD. In the past four years, research for UCDs has increased by 400%! Let's continue the momentum and end the devastating effects of UCD.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How is N-acetylglutamate synthase deficiency inherited? Are there any new research studies enrolling people with N-acetylglutamate synthase deficiency? How can I get my loved one seen at the National Institutes of Health? See answer


  1. N-acetylglutamate synthase deficiency. Genetics Home Reference. October 2006; http://ghr.nlm.nih.gov/condition=nacetylglutamatesynthasedeficiency.
  2. What is a Urea Cycle Disorder?. National Urea Cyle Disorders Foundation. http://www.nucdf.org/ucd.htm. Accessed 4/12/2017.
  3. Mew NA, Lanpher BC, Gropman A, Chapman KA, Simpson KL, Summar ML. Urea Cycle Disorders Overview. GeneReviews. April 9, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1217/.