Arginase Deficiency Medication

  • Author: Karl S Roth, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 5, 2012
 

Medication Summary

Long-term treatment of arginase deficiency is based on a low-protein diet and, possibly, administration of oral sodium benzoate or sodium phenylbutyrate.

Next

Endocrine and metabolic agents

Class Summary

The use of benzoate and phenylacetate is based on the need to provide alternate routes for disposition of waste nitrogen. Benzoate is transaminated to form hippuric acid, which is rapidly cleared by the kidney. Phenylacetate is converted to phenylacetyl coenzyme A (CoA) and then conjugated with glutamine to form phenylacetylglutamine. These 2 pathways result in disposition of 1 and 2 molecules of ammonia, respectively. Phenylbutyrate is more acceptable as a form of oral therapy because of a diminished odor but is not available for intravenous use.

View full drug information

Sodium benzoate and sodium phenylacetate (Ucephan, Ammonul)

 

Sodium benzoate combines with glycine to form hippurate, which is excreted in urine. One mol of benzoate removes 1 mol nitrogen. Sodium phenylacetate converted to phenylacetylglutamine, thereby taking up 1 mol per mol of free ammonia. The PO (Ucephan) and IV (Ammonul) products contain a combination of sodium benzoate 10 g/100 mL and sodium phenylacetate 10 g/100 mL (100 mg of each/mL).

View full drug information

Sodium phenylbutyrate (Buphenyl)

 

Prodrug rapidly converted PO to phenylacetylglutamine, which serves as substitute for urea and is excreted in the urine carrying 2 mol of nitrogen per mol of phenylacetylglutamine, assisting in clearance of nitrogenous waste.

Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

Karl S Roth, MD  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 Clinical 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, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research, Professor of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Faculty, Program in Molecular and Cellular Biosciences, Oregon Health and Science University School of Medicine; Attending Physician, Doernbecher Children's Hospital; Staff Consultant, Director of Metabolic Bone Disease Clinic, Shriners Hospital Portland

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, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

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.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Cederbaum SD, Yu H, Grody WW, et al. Arginases I and II: do their functions overlap?. Mol Genet Metab. Apr 2004;81 Suppl 1:S38-44. [Medline].

  2. Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Pediatr Neurol. Jan 2010;42(1):49-52. [Medline].

  3. Ash DE, Scolnick LR, Kanyo ZF, et al. Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. Mol Genet Metab. Aug 1998;64(4):243-9. [Medline].

  4. Scheuerle AE, McVie R, Beaudet AL, Shapira SK. Arginase deficiency presenting as cerebral palsy. Pediatrics. May 1993;91(5):995-6. [Medline].

  5. Morris SM Jr. Arginases and arginine deficiency syndromes. Curr Opin Clin Nutr Metab Care. Jan 2012;15(1):64-70. [Medline]. [Full Text].

  6. Brosnan ME, Brosnan JT. Orotic acid excretion and arginine metabolism. J Nutr. Jun 2007;137(6 Suppl 2):1656S-1661S. [Medline].

  7. Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr. Jan 2001;138(1 Pt 2):S56-S62. [Medline].

  8. Cederbaum SD, Shaw KN, Valente M. Hyperargininemia. J Pediatr. Apr 1977;90(4):569-73. [Medline].

  9. Cowley DM, Bowling FG, McGill JJ, et al. Adult-onset arginase deficiency. J Inherit Metab Dis. Aug 1998;21(6):677-8. [Medline].

  10. Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. Mar 2005;84(3):243-51. [Medline].

  11. Haberle J, Koch HG. Genetic approach to prenatal diagnosis in urea cycle defects. Prenat Diagn. May 2004;24(5):378-383. [Medline].

  12. Iyer R, Jenkinson CP, Vockley JG, et al. The human arginases and arginase deficiency. J Inherit Metab Dis. 1998;21 Suppl 1:86-100. [Medline].

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

  14. Korman SH, Gutman A, Stemmer E, Kay BS, Ben-Neriah Z, Zeigler M. Prenatal diagnosis fro arginase deficiency by second-trimester fetal erythrocyte arginase assay and first-trimester ARG1 mutation analysis. Prenat Diagn. Nov 2004;24(11):857-60. [Medline].

  15. Picker JD, Puga AC, Levy HL, et al. Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. J Pediatr. Mar 2003;142(3):349-52. [Medline].

  16. Qureshi IA, Letarte J, Ouellet R, Batshaw ML, et al. Treatment of hyperargininemia with sodium benzoate and arginine- restricted diet. J Pediatr. Mar 1984;104(3):473-6. [Medline].

  17. Saudubray JM, Rabier D. Biomarkers identified in inborn errors for lysine, arginine, and ornithine. J Nutr. Jun 2007;137(6 Suppl 2):1669S-1672S. [Medline].

  18. Scaglia F, Lee B. Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. Am J Med Genet C Semin Med Genet. May 15 2006;142(2):113-20. [Medline].

  19. Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr. Jan 2001;138(1 Suppl):S21-9. [Medline].

 
Previous
Next
 
Compounds that comprise the urea cycle are sequentially numbered, beginning with carbamyl phosphate (1). At this step, the first waste nitrogen is incorporated into the cycle; N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamoyl phosphate synthetase (CPS), in this step. 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 © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.