eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Ornithine Transcarbamylase Deficiency: Differential Diagnoses & Workup

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Sep 10, 2009

Differential Diagnoses

Arginase Deficiency
Methylmalonic Acidemia
Argininosuccinate Lyase Deficiency
N-Acetylglutamate Synthetase Deficiency
Carbamoyl Phosphate Synthetase Deficiency
Propionic Acidemia (Propionyl CoA Carboxylase Deficiency)
Citrullinemia
Sepsis
Hyperammonemia
Hyperammonemia-Hyperornithinemia-Homocitrullinemia Syndrome
Hyperinsulinemia

Other Problems to Be Considered

Organic acid disorders (eg, isovaleric acidemia)
Lysinuric protein intolerance
Transient hyperammonemia of the newborn
Hepatic insufficiency/dysfunction
Mitochondrial diseases and pyruvate carboxylase deficiency
Valproate ingestion
L -asparaginase ingestion
Reye syndrome

Workup

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.

Other Tests

  • Enzymatic deficiency of the ornithine transcarbamylase enzyme can be further confirmed using 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. 

More on Ornithine Transcarbamylase Deficiency

Overview: Ornithine Transcarbamylase Deficiency
Differential Diagnoses & Workup: Ornithine Transcarbamylase Deficiency
Treatment & Medication: Ornithine Transcarbamylase Deficiency
Follow-up: Ornithine Transcarbamylase Deficiency
Multimedia: Ornithine Transcarbamylase Deficiency
References
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References

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Further Reading

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Keywords

ornithine transcarbamylase deficiency, OTC deficiency, ornithine carbamoyltransferase deficiency, OTCD, urea cycle disorder, hyperammonemia, N -acetylglutamate, carbamyl phosphate, citrulline, mental retardation, papilledema, tachypnea, hyperpnea, apnea

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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: MDS Pharma Salary Employment

Medical Editor

Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director: Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA).
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: Genzyme Honoraria Speaking and teaching; Genzyme Grant/research funds Other; Shire Honoraria Speaking and teaching; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Speaking and teaching; Biomarin Consulting fee Consulting; Amicus  Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leonard G Feld, MD, PhD, MMM, FAAP, Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center
Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

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 of Genetics, Munroe Meyer Institute, Professor, Department of Pediatrics, Pathology and Microbiology, 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.

 
 
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