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N-Acetylglutamate Synthetase Deficiency Workup

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
Updated: Nov 17, 2014

Laboratory Studies

See the list below:

  • Affected newborns may experience fulminant hyperammonemia, which remains undetected unless index of suspicion is high.
  • No routine laboratory tests provide definitive clues.
    • The BUN level may be low, but this is an unreliable index of high blood ammonia.
    • A respiratory alkalosis may be present.
    • Urine orotic acid levels are within reference ranges.
  • Plasma alanine and glutamine levels are elevated.
  • Urine amino acids are nondiagnostic in N- acetylglutamate synthetase (NAGS) deficiency but are important in order to help rule out hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) or lysinuric protein intolerance (LPI) (see Differentials).
  • Urine organic acids are within reference ranges in NAGS deficiency. Ruling out organic acid disorders, which can present with similar signs and symptoms and hyperammonemia, is important.
  • Definitive diagnosis rests with DNA sequencing; to date, there is no newborn metabolic screen which can detect the defect.

Imaging Studies

See the list below:

  • Imaging studies generally are not helpful, with the exception of brain imaging when cerebral edema is suspected. Documenting a finding of cerebral edema is important.


See the list below:

  • DNA sequencing is available in selected laboratories; mutation analysis provides a definitive diagnosis
Contributor Information and Disclosures

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Uri S Alon, MD Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children's Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine

Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research

Disclosure: Nothing to disclose.

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Compounds comprising the urea cycle are numbered sequentially, beginning with carbamyl phosphate (1). At this step, the first waste nitrogen is incorporated into the cycle; at this step, N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamyl phosphate synthetase (CPS). Compound 2 is citrulline, the product of condensation between carbamyl phosphate (1) and ornithine (8); the mediating enzyme is ornithine transcarbamylase. Compound 3 is aspartic acid, which is combined with citrulline to form argininosuccinic acid (ASA) (4); the reaction is mediated by ASA synthetase. Compound 5 is fumaric acid generated in the reaction that converts ASA to arginine (6), which is mediated by ASA lyase.
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