Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene

Human Mutation
Ljubica CaldovicMendel Tuchman


N-acetylglutamate synthase (NAGS) deficiency, an autosomal recessive disorder, is the last urea cycle disorder for which molecular testing became available. This is the first comprehensive report of 21 mutations that cause NAGS deficiency and of commonly found polymorphisms in the NAGS gene. Five mutations are reported here for the first time. A total of 10 disease-causing mutations are associated with acute neonatal hyperammonemia; the remaining mutations were found in patients with late onset disease. Residual enzymatic activities are included in this report and the deleterious effects of eight mutations were confirmed by expression studies. Mutations in the NAGS gene are distributed throughout its reading frame. No mutations have been found in exon 1, which encodes for the putative mitochondrial targeting signal and variable segment of NAGS. Three polymorphisms have been found. Early, accurate, and specific diagnosis of NAGS deficiency is critical since this condition can be successfully treated with N-carbamylglutamate (NCG, Carbaglu; Orphan Europe). Treatment with NCG should be initiated as soon as a patient is suspected of having NAGS deficiency. Molecular testing represents the most reliable method of diagnosis.


Mar 1, 1978·European Journal of Biochemistry·K Shigesada, M Tatibana
Jan 1, 1992·Journal of Inherited Metabolic Disease·A B BurlinaF Zacchello
Jan 1, 1991·Journal of Inherited Metabolic Disease·A L PandyaJ C Williams
Jun 1, 1990·European Journal of Pediatrics·O N ElpelegH Hurvitz
Jan 1, 1988·Journal of Inherited Metabolic Disease·C BachmannJ P Colombo
May 1, 1982·Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Für Klinische Chemie Und Klinische Biochemie·J P ColomboP Aeberhard
Jan 1, 1982·Advances in Experimental Medicine and Biology·C BachmannK Jaggi
Jan 1, 1995·Journal of Inherited Metabolic Disease·N GuffonP Guibaud
Jan 14, 1998·Journal of Inherited Metabolic Disease·J HinnieF J Dryburgh
Dec 31, 1998·Journal of Inherited Metabolic Disease·A A MorrisJ V Leonard
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Jun 7, 2002·The Biochemical Journal·Ljubica CaldovicMendel Tuchman
Nov 26, 2002·Annals of Neurology·Orly ElpelegClaude Bachmann
Dec 3, 2002·Biochemical and Biophysical Research Communications·Ljubica CaldovicMendel Tuchman
May 20, 2003·Human Mutation·Johannes HäberleHans Georg Koch
May 28, 2004·Prenatal Diagnosis·Johannes Häberle, Hans Georg Koch
Oct 14, 2004·The Journal of Pediatrics·Ljubica CaldovicMendel Tuchman
Feb 17, 2005·Human Mutation·Ljubica CaldovicMendel Tuchman
Aug 30, 2005·The Journal of Pediatrics·Nathalie GuffonChristine Vianey-Saban
Jun 1, 1999·Nutrition Research Reviews·J C Waterlow

❮ Previous
Next ❯


Mar 16, 2011·International Journal of General Medicine·Marta DaniottiLuca Filippi
Dec 20, 2012·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·A CartagenaC Prasad
Mar 23, 2010·Molecular Genetics and Metabolism·Ljubica CaldovicMendel Tuchman
Feb 10, 2009·Lancet·J V Leonard, S Richmond
Aug 28, 2012·Metabolism: Clinical and Experimental·Maria M AdevaCristóbal Donapetry
Jul 16, 2011·Biochimica Et Biophysica Acta·Barbara RengaStefano Fiorucci
Dec 25, 2012·Biochemical and Biophysical Research Communications·Gengxiang ZhaoDashuang Shi
May 1, 2012·Expert Review of Endocrinology & Metabolism·Johannes Häberle
Oct 12, 2019·Journal of Inherited Metabolic Disease·Lynne RumpingNanda M Verhoeven-Duif
Jan 24, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Gengxiang ZhaoDashuang Shi
Apr 16, 2019·Journal of Inherited Metabolic Disease·Johannes HäberleCarlo Dionisi-Vici
Jan 1, 2016·Expert Review of Endocrinology & Metabolism·Cristel C Chapel-CrespoKimihiko Oishi
Oct 11, 2020·Orphanet Journal of Rare Diseases·Aileen Kenneson, Rani H Singh

❮ Previous
Next ❯

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.


Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.