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Genetics Home Reference: your guide to understanding genetic conditions
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N-acetylglutamate synthase deficiency

Reviewed October 2006

What is N-acetylglutamate synthase deficiency?

N-acetylglutamate synthase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

N-acetylglutamate synthase deficiency may become evident in the first few days of life. An infant with this condition may be lacking in energy (lethargic) or unwilling to eat, and have a poorly controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications of N-acetylglutamate synthase deficiency may include developmental delay and intellectual disability.

In some affected individuals, signs and symptoms of N-acetylglutamate synthase deficiency are less severe, and do not appear until later in life. Some people with this form of the disorder cannot tolerate high-protein foods such as meat. They may experience sudden episodes of ammonia toxicity, resulting in vomiting, lack of coordination, confusion or coma, in response to illness or other stress.

How common is N-acetylglutamate synthase deficiency?

N-acetylglutamate synthase deficiency is a very rare disorder. Only a few cases have been reported worldwide, and the overall incidence is unknown.

What genes are related to N-acetylglutamate synthase deficiency?

Mutations in the NAGS gene cause N-acetylglutamate synthase deficiency.

N-acetylglutamate synthase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

The NAGS gene provides instructions for making the enzyme N-acetylglutamate synthase, which helps produce a compound called N-acetylglutamate. This compound is needed to activate another enzyme, carbamoyl phosphate synthetase I, which controls the first step of the urea cycle.

In people with N-acetylglutamate synthase deficiency, N-acetylglutamate is not available in sufficient quantities, or is not present at all. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. This accumulation of ammonia causes the neurological problems and other signs and symptoms of N-acetylglutamate synthase deficiency.

Related Gene(s)

Changes in this gene are associated with N-acetylglutamate synthase deficiency.

  • NAGS

How do people inherit N-acetylglutamate synthase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of N-acetylglutamate synthase deficiency?

These resources address the diagnosis or management of N-acetylglutamate synthase deficiency and may include treatment providers.

  • Gene Review: Urea Cycle Disorders Overview (http://www.ncbi.nlm.nih.gov/books/NBK1217)
  • Genetic Testing Registry: Hyperammonemia, type III (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268543)
  • MedlinePlus Encyclopedia: Hereditary Urea Cycle Abnormality (http://www.nlm.nih.gov/medlineplus/ency/article/000372.htm)

You might also find information on the diagnosis or management of N-acetylglutamate synthase deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about N-acetylglutamate synthase deficiency?

You may find the following resources about N-acetylglutamate synthase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for N-acetylglutamate synthase deficiency?

  • hyperammonemia, type III
  • N-acetylglutamate synthetase deficiency
  • NAGS deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about N-acetylglutamate synthase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding N-acetylglutamate synthase deficiency?

ammonia ; autosomal ; autosomal recessive ; cell ; class ; coma ; compound ; deficiency ; developmental delay ; disability ; enzyme ; gene ; hyperammonemia ; incidence ; inherited ; lacking in energy ; lethargic ; nervous system ; neurological ; phosphate ; protein ; recessive ; stress ; toxic ; urea

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Caldovic L, Morizono H, Panglao MG, Cheng SF, Packman S, Tuchman M. Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Hum Genet. 2003 Apr;112(4):364-8. Epub 2003 Feb 20. (http://www.ncbi.nlm.nih.gov/pubmed/12594532?dopt=Abstract)
  • Caldovic L, Morizono H, Panglao MG, Lopez GY, Shi D, Summar ML, Tuchman M. Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles. Hum Mutat. 2005 Mar;25(3):293-8. (http://www.ncbi.nlm.nih.gov/pubmed/15714518?dopt=Abstract)
  • Elpeleg O, Shaag A, Ben-Shalom E, Schmid T, Bachmann C. N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845-9. (http://www.ncbi.nlm.nih.gov/pubmed/12447942?dopt=Abstract)
  • Häberle J, Schmidt E, Pauli S, Kreuder JG, Plecko B, Galler A, Wermuth B, Harms E, Koch HG. Mutation analysis in patients with N-acetylglutamate synthase deficiency. Hum Mutat. 2003 Jun;21(6):593-7. (http://www.ncbi.nlm.nih.gov/pubmed/12754705?dopt=Abstract)
  • OMIM: N-ACETYLGLUTAMATE SYNTHASE DEFICIENCY (http://omim.org/entry/237310)
  • Schmidt E, Nuoffer JM, Häberle J, Pauli S, Guffon N, Vianey-Saban C, Wermuth B, Koch HG. Identification of novel mutations of the human N-acetylglutamate synthase gene and their functional investigation by expression studies. Biochim Biophys Acta. 2005 Apr 15;1740(1):54-9. Epub 2005 Feb 24. (http://www.ncbi.nlm.nih.gov/pubmed/15878741?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2006
Published: December 16, 2014