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

Ornithine Transcarbamylase Deficiency: Treatment & Medication

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

Updated: Sep 10, 2009

Treatment

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

Consultations

  • 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.

Medication

Metabolic agents

These agents assist in the excretion of nitrogen and serve as an alternative to urea to reduce waste nitrogen levels. Administer only in a large medical facility with close laboratory monitoring available.


Arginine (R-Gene 10)

Enhances production of ornithine, which facilitates incorporation of waste nitrogen into the formation of citrulline and argininosuccinate. Provides 1 mol of urea plus 1 mol ornithine per mol arginine when cleaved by arginase. Pituitary stimulant for the release of human growth hormone (HGH). Often induces pronounced HGH levels in patients with intact pituitary function.

Adult

Not established

Pediatric

Hyperammonemic crisis: 0.66 g/kg/dose IV infused over 24 h; dilute in 25-35 mL dextrose 10%
Maintenance treatment in a stable child: (administer as the free base) 0.4-0.7 g/kg/d PO

Coadministration with amphotericin, triamterene, amiloride, or spironolactone may increase risk of hyperkalemia

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Renal impairment; diagnostic aid not intended for therapeutic use; may cause nausea, vomiting, headache, hyperkalemia, hyperglycemia, or venous irritation during IV administration


Sodium phenylacetate and sodium benzoate (Ammonul)

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 CPS, OTC, ASS, or ASL 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.

Adult

Loading dose: 55 mL (5.5 g)/m2 IV over 90-120 min via central line
Maintenance dose: 55 mL (5.5 g)/m2/d IV over 24 h via central line
Must dilute IV dose in at least 25 mL/kg of dextrose 10% before administration

Pediatric

Ammonul:
<20 kg:
Loading dose: 2.5 mL (250 mg)/kg IV over 90-120 min via central line
Maintenance dose: 2.5 mL (250 mg)/kg/d IV over 24 h via central line
Must dilute IV dose in at least 25 mL/kg of dextrose 10% before administration
>20 kg: Administer as in adults

Penicillin may decrease effects of sodium benzoate/sodium phenylacetate; probenecid may inhibit renal excretion of products of sodium benzoate and sodium phenylacetate; valproate may antagonize efficacy of sodium benzoate and sodium phenylacetate; corticosteroids may increase body protein metabolism, thereby increasing plasma ammonia levels; do not use concomitantly with oral sodium phenylbutyrate (Buphenyl) due to additive effects

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution when administering to patients with neonatal hyperbilirubinemia (competes for bilirubin binding sites on albumin); because of sodium content, exercise caution when giving to patients with congestive heart failure, severe renal dysfunction, and sodium retention with edema; common adverse effects include nausea, vomiting, tinnitus, and visual disturbance; IV must be diluted with dextrose 10% and administered via central line; phenylacetate may cause neurotoxicity; typically administered with antiemetic to prevent common occurrence of nausea and vomiting; caution in severe congestive heart failure or severe renal insufficiency since it contains large amount of sodium (30.5 mg/mL in undiluted IV product)

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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