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Disease Profile

Ornithine transcarbamylase deficiency

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 100 000

US Estimated

Europe Estimated

Age of onset

All ages





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Ornithine carbamoyltransferase deficiency; OTC deficiency; OTCD


Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;


Ornithine transcarbamylase (OTC) deficiency is a genetic disease that causes too much ammonia to accumulate in the blood (hyperammonemia). Ammonia is toxic when levels are too high and especially affects the nervous system.

Severe OTC deficiency (the early-onset form) typically affects males (and rarely females) and causes symptoms in the newborn period or early childhood. Signs and symptoms of this form may include lack of energy and appetite, poorly-controlled breathing rate and body temperature, unusual body movements, seizures, or coma. When not treated, the disease can lead to development delay, intellectual disability, and liver damage. Less frequently, symptoms of OTC deficiency begin later in life (the late-onset form) and are less severe. This form occurs in both males and females. Symptoms of this form may include episodes of delirium, erratic behavior, a reduced level of consciousness, headaches, vomiting, and seizures.[1]

OTC is caused by mutations in the OTC gene and inheritance is X-linked.[1] Treatment involves removing protein from the diet, taking certain medications, and having hemodialysis if needed for extremely high blood ammonia levels.[2]


Most commonly, symptoms of OTC deficiency begin in infancy (the early-onset form). An infant with OTC deficiency may be lacking energy (lethargic), be unwilling to eat, and have problems with breathing rate or body temperature. Some babies with OTC deficiency experience seizures, unusual body movements, or go into a coma. If not treated, this form can lead to complications including developmental delayintellectual disability, progressive liver damage, skin problems, and brittle hair.[1][3] Symptoms may be triggered by eating foods high in protein, illness, or steroid medications.[3]

In some people with OTC deficiency, signs and symptoms are less severe and do not begin until later in life (the late-onset form). Symptoms are triggered by a build-up of ammonia and may include:[1]

  • Episodes of delirium, erratic behavior, or reduced consciousness.
  • Headaches.
  • Vomiting.
  • An aversion to foods high in protein.
  • Seizures.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

Hepatic failure
Liver failure
High blood ammonia levels
Low blood sugar
Pyloric stenosis
Increased spleen size
5%-29% of people have these symptoms
Percent of people who have these symptoms is not available through HPO
Cerebral edema
Swelling of brain
Episodic ammonia intoxication
Episodic ataxia
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Global developmental delay
High plasma glutamine
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Low plasma citrulline
Protein avoidance
Respiratory alkalosis
Throwing up
X-linked recessive inheritance


OTC deficiency belongs to a group of genetic diseases that affect the urea cycle (urea cycle disorders). It is caused by mutations in the OTC gene. This gene gives the body instructions for making the OTC enzyme.

The urea cycle is a chain of reactions in liver cells, which processes the nitrogen that is left over when protein is used by the body. It uses the nitrogen to make urea, which is then eliminated by the kidneys. The OTC enzyme is needed for a specific reaction in the urea cycle. Mutations in the OTC gene impair the OTC enzyme's ability to function. This causes nitrogen to build up in the blood, in the form of ammonia. The toxicity of the ammonia in the blood damages the nervous system and causes the features of OTC deficiency.[1]


Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    Management Guidelines

    • GeneReviews provides a current, expert-authored, peer-reviewed, full-text article urea cycle disorders in general that you may find helpful. GeneReview articles describe the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
    • The NORD Physician Guide for Ornithine transcarbamylase deficiency was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.
    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

      • Glycerol phenylbutyrate(Brand name: Ravicti) Manufactured by Horizon Pharma, Inc.
        FDA-approved indication: Use as a nitrogen-binding adjunctive therapy for chronic management of adult and pediatric patients at least 2 months of age with urea cycle disorders (UCDs) that cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements).
        National Library of Medicine Drug Information Portal


      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus.gov provides more information on urea cycle disorders in general. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.
        • Genetics Home Reference (GHR) contains information on Ornithine transcarbamylase deficiency. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Ornithine transcarbamylase deficiency. Click on the link to view a sample search on this topic.

            Selected Full-Text Journal Articles


              1. Ornithine transcarbamylase deficiency. Genetics Home Reference. 2017; https://www.ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency.
              2. Roth KS. Ornithine Transcarbamylase Deficiency. Medscape Reference. 2016; https://emedicine.medscape.com/article/950672-overview.
              3. Ornithine Transcarbamylase (OTC) Deficiency. New England Consortium of Metabolic Programs. September 8, 2013; https://newenglandconsortium.org/for-families/transitioning-teens-to-young-adults/transition-toolkit/metabolic-condition-basics/ornithine-transcarbamylase-otc-deficiency/.

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