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Ornithine Transcarbamylase Deficiency Follow-up

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Aug 28, 2015
 

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.

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Prognosis

Most affected male infants with neonatal presentation have not escaped the initial episode with normal mentation. Nonetheless, survival for many years can be achieved with very careful monitoring; use of oral citrulline, benzoate, and phenylacetate; and scrupulous dietary attention.

Prognosis for older males with initial onset remains unclear because so many remain undiagnosed until very late in the clinical course.

Most heterozygous females appear to be relatively healthy, except for a propensity to develop severe headaches with high protein intake. Women and children who are mildly affected can have an excellent prognosis with proper care.

The long-term outlook for individuals with all forms of OTC deficiency is guarded, particularly with reference to cerebral function.[13]

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Patient Education

Family pedigree studies in this disease are essential for the following 2 reasons:

  • The X-linked nature of the mutation leads to a 1:2 chance of recurrence in any subsequent male conceptus if the mother is a carrier.
  • All female siblings of the obligate heterozygous maternal carrier are potential carriers, whereas male siblings may be at risk for late-onset presentation. The second reason is derived from the first.

Another compelling issue in family counseling is the overwhelming sense of guilt with which the carrier mother must deal.

Finally, repeatedly reinforce the parents in their abilities to perceive early signs of hyperammonemia and to take immediate steps to obtain medical care. Prenatal diagnosis is possible.

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Contributor Information and Disclosures
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, 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 Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD 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 Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

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 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: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

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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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