Sections

Argininosuccinate Lyase (ASL) Deficiency

Sections Argininosuccinate Lyase (ASL) Deficiency
Overview
Presentation
- History
- Physical
- Causes
- Complications
- Show All
DDx
Workup
Treatment
Medication
References

Medication

Medication Summary

Because the enzyme defect interrupts the urea cycle, alternative means of waste nitrogen disposal are required. Some medications assist in excreting nitrogen and serve as an alternative to urea to reduce waste nitrogen levels. Administer only in a large medical facility with close laboratory monitoring.

Class Summary

These are used in management of severe, uncompensated metabolic alkalosis.

Arginine (R-Gene)

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Enhances production of ornithine, which facilitates incorporation of waste nitrogen into the formation of citrulline and ASA.

Sodium phenylacetate and sodium benzoate (Ammonul)

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Benzoate combines with glycine to form hippurate, which is excreted in urine. One mol of benzoate removes 1 mol of nitrogen. Phenylacetate conjugates (via acetylation) glutamine in the liver and kidneys to form phenylacetylglutamine, which is excreted by the kidneys. The nitrogen content of phenylacetylglutamine per mol is identical to that of urea (2 mol of nitrogen). Ammonul must be administered with arginine for carbamyl phophate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or ASA lyase deficiencies. Indicated as adjunctive treatment of acute hyperammonemia associated with encephalopathy caused by urea cycle enzyme deficiencies. Serves as an alternative to urea to reduce waste nitrogen levels.

Glycerol phenylbutyrate (Ravicti)

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Glycerol phenylbutyrate is a nitrogen-binding agent for chronic management of adult and pediatric patients (including newborns) with urea cycle disorders who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. It is a pre-prodrug that is metabolized by ester hydrolysis and pancreatic lipases to phenylbutyrate and then by beta oxidation to phenylacetate. Glutamine is conjugated with phenylacetate to form phenylacetylglutamine, a nitrogen waste product that is excreted in the urine. It is not indicated for treatment of hyperammonemia.

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Media Gallery

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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Author

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, The Scientific Research Honor Society, 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, FAAP, FACMG Professor (Clinical), Department of Pediatrics, University of Wisconsin School of Medicine and Public Health; Editor-in-Chief, Genetics in Medicine; Chief Medical Officer, PreventionGenetics

Robert D Steiner, MD, FAAP, FACMG 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: PreventionGenetics, ACMG, Acer Therapeutics, Biomarin; Best Doctors, Health Advances, Precision for Health, PTC Therapeutics, CTX Alliance, Aeglea, Eton, Leadiant<br/>Serve(d) as a speaker or a member of a speakers bureau for: France Foundation, Medscape<br/>Received research grant from: Alexion<br/>Received income in an amount equal to or greater than $250 from: Marshfield Clinic, France Foundation, Medscape, PreventionGenetics, ACMG, Acer Therapeutics; Raptor, Retrophin/Travere, Censa; Biomarin; Best Doctors, Health Advances, Precision for Health, PTC Therapeutics, Aeglea, Leadiant<br/>Travel Support for: CTX Alliance.

Sections Argininosuccinate Lyase (ASL) Deficiency
Overview
Presentation
- History
- Physical
- Causes
- Complications
- Show All
DDx
Workup
Treatment
Medication
References

Argininosuccinate Lyase (ASL) Deficiency Medication

Medication Summary

Urea Cycle Disorder Treatment Agents

Class Summary

Arginine (R-Gene)

Arginine (R-Gene)

Sodium phenylacetate and sodium benzoate (Ammonul)

Sodium phenylacetate and sodium benzoate (Ammonul)

Glycerol phenylbutyrate (Ravicti)

Glycerol phenylbutyrate (Ravicti)

Argininosuccinate Lyase (ASL) Deficiency Medication

Medication Summary

Urea Cycle Disorder Treatment Agents

Class Summary

Arginine (R-Gene)

Arginine (R-Gene)

Sodium phenylacetate and sodium benzoate (Ammonul)

Sodium phenylacetate and sodium benzoate (Ammonul)

Glycerol phenylbutyrate (Ravicti)

Glycerol phenylbutyrate (Ravicti)

References

Tables

Contributor Information and Disclosures

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