Medical Care

Immediate temporary discontinuation of protein intake in a symptomatic individual with ornithine transcarbamylase (OTC) deficiency is mandatory, with compensatory increases in carbohydrates and lipids in order to offset any catabolic tendency to draw on muscle amino acids for energy.

In a patient who is comatose with extremely high blood ammonia levels (in some cases exceeding 2000 mg/dL), rapid reduction can be achieved with hemodialysis.

Intravenous administration of sodium benzoate, arginine, and sodium phenylacetate is important; however, only administer these drugs in a large medical facility setting with close laboratory monitoring available. Intravenous sodium benzoate and phenylacetate (Ammonul) was approved in the United States in February 2005.

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.^[11]In a separate study involving young children ages 2 months through 5 years, glycerol phenylbutyrate resulted in a more evenly distributed urinary output of phenylacetylglutamine (PAGN) over 24 hours and accounted for fewer symptoms from accumulation of phenylacetate.^[12]

A biochemical geneticist and a highly trained nutritionist should administer long-term outpatient care in a large facility setting with laboratory monitoring available.

Consultations

Consultations include the following:

Medical geneticist
Metabolic disease specialist
Dietitian

Diet

Immediate temporary discontinuation of protein intake in a symptomatic individual is mandatory, with compensatory increases in carbohydrates and lipids in order to offset any catabolic tendency to draw on muscle amino acids for energy.

A highly trained nutritionist should administer long-term outpatient care in a large facility setting with laboratory monitoring available.

Scrupulous adherence to the dietary and medication recommendations is mandatory for survival.

Further Outpatient Care

A biochemical geneticist must oversee patient care because the metabolic integrity of such individuals with ornithine transcarbamylase (OTC) deficiency is very tenuously poised.

Proper nutrition does not follow the usual nutritional rules, and any variations from what is appropriate may result in disaster. This is true throughout life but mostly in the growing infant and adolescent child in whom requirements may fluctuate weekly and must be closely monitored.

Scrupulous adherence to the dietary and medication recommendations is mandatory for survival. Under no circumstances should this be undertaken by a general physician without close guidance from an expert in the care of patients with inherited metabolic diseases.

Medication

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Finkelstein JE, Hauser ER, Leonard CO, Brusilow SW. Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr. 1990 Dec. 117(6):897-902. [QxMD MEDLINE Link].
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Media Gallery

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; during this step, N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamoyl phosphate synthetase (CPS). Compound 2 is citrulline, which is 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

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

Luis O Rohena, MD, PhD, FAAP, FACMG 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

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-part of Exact Sciences; Acer Therapeutics; DNARx; Best Doctors; PTC Therapeutics; CTX Alliance; Leadiant' Travere<br/>Received income in an amount equal to or greater than $250 from: Marshfield Clinic; PreventionGenetics-part of Exact Sciences; Acer Therapeutics; PTC Therapeutics; DNARx; Leadiant; Travere.

Sections Ornithine Transcarbamylase (OTC) Deficiency
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Ornithine Transcarbamylase (OTC) Deficiency Treatment & Management

Medical Care

Consultations

Diet

Further Outpatient Care

References

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