Laboratory Studies

In an individual with ornithine transcarbamylase (OTC) deficiency, the sine qua non of diagnosis is demonstration of hyperammonemia.

As in CPS deficiency, routinely obtained blood chemistries are not helpful, although a very low BUN level may present a diagnostic clue. This should not be interpreted as a substitute for blood ammonia studies because it is not sufficiently reliable.

Liver and kidney function typically remain normal unless hypoxia or shock supervenes. However, exceptions have been noted.

Serum amino acid quantitation may show elevated ornithine, glutamine, and alanine levels and relatively low citrulline levels, but these changes are neither invariable nor diagnostic. Urine organic acid and amino acid analysis are helpful in ruling out other conditions.

Beyond demonstration of hyperammonemia, the only basis for clinical diagnosis is demonstration of elevated urinary orotic acid. This test also can be used, under appropriate conditions, to detect asymptomatic carriers.

Remember that ornithine transcarbamylase is a mitochondrial hepatic enzyme and is subject to rapid postmortem degradation. Therefore, perform any liver biopsy prior to or immediately after death and properly handle the specimen in order to avoid artifactual diagnosis of deficiency. Experienced diagnostic laboratories perform control assays of nonlabile hepatic enzymes, but this cannot substitute for proper sampling and handling. Hepatic biopsy and enzyme analysis have been replaced by mutational analysis, thus reducing the risk to the affected infant.

Other Tests

Enzymatic deficiency of the ornithine transcarbamylase enzyme has been supplanted by molecular diagnosis. However, even using a combination of different molecular analytic strategies, only 80% of proven enzymatic deficiencies can be shown to have genetic mutation.

The reasons for this inconsistency remain elusive. However, molecular techniques are very useful for prenatal diagnosis, especially when the specific mutation in the pedigree has been previously documented.

Treatment & Management

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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 Workup

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