Medscape is available in 5 Language Editions – Choose your Edition here.


Carbamoyl Phosphate Synthetase Deficiency Treatment & Management

  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
Updated: Aug 24, 2015

Medical Care

Depending on clinical status and the blood ammonia level, the logical first step is to reduce protein intake and to attempt to maintain energy intake. Initiate intravenous infusion of 10% glucose (or higher, if administered through a central line) and lipids.

Intravenous sodium benzoate and sodium phenylacetate may be helpful. Arginine is usually administered with benzoate and phenylacetate. This is best administered in the setting of a major medical center where facilities for hemodialysis in infants is available.

Glycerol phenylbutyrate is a pre-prodrug that undergoes metabolism to form phenylacetate. Results of a phase 3 study comparing ammonia control in adults showed glycerol phenylbutyrate was noninferior to sodium phenylbutyrate.[8] In a separate study involving young children ages 2 months through 5 years, glycerol phenylbutyrate resulted in a more evenly distributed urinary output of PAGN over 24 hours and accounted for fewer symptoms from accumulation of phenylacetate.[9]

In patients with an extremely high blood ammonia level, rapid treatment with hemodialysis is indicated.

Metabolic disease specialists should provide long-term care with very close and frequent follow-up.



See the list below:

  • Medical geneticist
  • Metabolic disease specialist
  • Dietitian


An appropriate diet must meet minimal protein requirements for growth and must include scrupulous monitoring.

These requirements change with age, and caloric needs must also be met in order to appropriately use the requisite protein.

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.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

  1. Yefimenko I, Frequet V, Marco-Marin C, et al. Understanding carbomyl phosphate synthetase deficiency: impact of clinical mutations on enzyme functionality. J Mol Biol. 2005. 349:127-141.

  2. Diez-Fernandez C, Hu L, cervera J, et al. Understanding carbomyl phosphate synthetase (CPS1) deficiency by using the recombinantly purified human enzyme: effects of CPS1 mutations that concentrate in a central domain of unknown function. Mol Genet Metab. June 2014. 112:123-132. [Medline].

  3. Keskinen P, Siitonen A, Salo M. Hereditary urea cycle diseases in Finland. Acta Paediatr. 2008 Oct. 97(10):1412-9. [Medline].

  4. Funghini S, Thusberg J, Spada M, Gasperini S, Parini R, Ventura L, et al. Carbamoyl phosphate synthetase 1 deficiency in Italy: clinical and genetic findings in a heterogeneous cohort. Gene. 2012 Feb 10. 493(2):228-34. [Medline].

  5. Wong LJ, Craigen WJ, O'Brien WE. Postpartum coma and death due to carbamoyl-phosphate synthetase I deficiency. Ann Intern Med. 1994 Feb 1. 120(3):216-7. [Medline].

  6. Gunz AC, Choong K, Potter M, et al. Magnetic resonance imaging findings and neurodevelopmental outcomes in neonates with urea-cycle defects. Int Med Case Rep J. August 2013. 6:41-48. [Medline].

  7. Häberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, et al. Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations. Hum Mutat. 2011 Jun. 32(6):579-89. [Medline].

  8. Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2012 Sep 7. [Medline]. [Full Text].

  9. Smith W, Diaz GA, Lichter-Konecki U, Berry SA, Harding CO, McCandless SE, et al. Ammonia Control in Children Ages 2 Months through 5 Years with Urea Cycle Disorders: Comparison of Sodium Phenylbutyrate and Glycerol Phenylbutyrate. J Pediatr. 2013 Jan 13. [Medline].

  10. Batshaw ML, Brusilow S, Waber L, Blom W, et al. Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion. N Engl J Med. 1982 Jun 10. 306(23):1387-92. [Medline].

  11. Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr. 2001 Jan. 138(1 Suppl):S56-60; discussion S60-1. [Medline].

  12. Eather G, Coman D, Lander C, et al. Carbamyl phosphate synthase deficiency: diagnosed during pregnancy in a 41-year-old. J Clin Neurosci. 2006. 13:702-6.

  13. Eeds AM, Hall LD, Yadav M, et al. The frequent observation of evidence for nonsense-mediated decay in RNA from patients with caramyl phosphate synthetase I deficiency. Mol Genet Metab. 2006. 89:80-86.

  14. Farriaux JP, Ponte C, Pollitt RJ, Lequien P, et al. Carbamyl-phosphate-synthetase deficiency with neonatal onset of symptoms. Acta Paediatr Scand. 1977 Jul. 66(4):529-34. [Medline].

  15. Finckh U, Kohlschutter A, Schafer H, Sperhake K, et al. Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat. 1998. 12(3):206-11. [Medline].

  16. Freeman JM, Nicholson JF, Schimke RT, Rowland LP, et al. Congenital hyperammonemia. Association with hyperglycinemia and decreased levels of carbamyl phosphate synthetase. Arch Neurol. 1970 Nov. 23(5):430-7. [Medline].

  17. Gropman AL, Summar M, Leonard JV. Neurological implications of urea cycle disorders. J Inherit Metab Dis. 2007 Nov. 30(6):865-79. [Medline].

  18. Kojic J, Robertson PL, Quint DJ. Brain glutamine by MRS in a patient with urea cycle disorder and coma. Pediatr Neurol. 2005. 32:143-146.

  19. Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr. 2001 Jan. 138(1 Pt 2):S21-S29.

  20. Summar ML. Molecular genetic research into carbamoyl-phosphate synthase I: molecular defects and linkage markers. J Inherit Metab Dis. 1998. 21 Suppl 1:30-9. [Medline].

  21. Summar ML, Hall L, Christman B. Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Mol Genet Metab. 2004. 81Supplement 1:S12-S19.

  22. Verbiest HB, Straver JS, Colombo JP, van der Vijver JC, et al. Carbamyl phosphate synthetase-1 deficiency discovered after valproic acid-induced coma. Acta Neurol Scand. 1992 Sep. 86(3):275-9. [Medline].

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.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.