National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Ornithine transcarbamylase deficiency

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]
Last updated: 7/21/2017
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 delay, intellectual 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.
Last updated: 7/21/2017

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine
[ more ] 		0003355
Hepatic failure
Liver failure
0001399
Hyperammonemia
High blood ammonia levels
0001987
Hypoglycemia
Low blood sugar
0001943
Pyloric stenosis 0002021
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Stroke 0001297
Percent of people who have these symptoms is not available through HPO
Ataxia 0001251
Cerebral edema
Swelling of brain
0002181
Coma 0001259
Episodic ammonia intoxication 0001951
Episodic ataxia 0002131
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Global developmental delay 0001263
Hyperglutaminemia
High plasma glutamine
0003217
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Irritability
Irritable
0000737
Lethargy 0001254
Low plasma citrulline 0003572
Protein avoidance 0002038
Respiratory alkalosis 0001950
Seizure 0001250
Vomiting
Throwing up
0002013
X-linked recessive inheritance 0001419
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Last updated: 7/1/2020
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]
Last updated: 7/21/2017
OTC deficiency follows X-linked inheritance.[1] This is because the gene responsible for causing OTC deficiency is located on the X chromosome, one of the two sex chromosomes.

X-linked diseases more commonly occur in males, who have only one X chromosome (and one Y chromosome). Having a mutation in a gene on their X chromosome is enough to cause the disease. Females have two X chromosomes, so if they have a mutation on one of them, they still have one X chromosome without the mutation and are much less likely to have the disease. In some cases however, females with only one mutation in the OTC gene will have symptoms of OTC deficiency. Females with mutations in the gene on both chromosomes will have the disease. 

If a mother has a mutation that causes OTC deficiency and the father does not, the risk to each of her children depends on whether they are male or female.
  • Each son has a 50% chance to inherit the mutation and have OTC deficiency.
  • Each daughter has a 50% chance to inherit the mutation and may or may not develop symptoms, like the mother.
If a father has OTC deficiency and the mother does not have a mutation, all sons will not inherit the mutation, and all daughters will inherit the mutation. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[1]

People with personal questions about the inheritance of this condition are encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:
  • Thoroughly evaluating the family history.
  • Addressing questions and concerns.
  • Assessing recurrence risks.
  • Facilitating genetic testing if desired.
  • Discussing reproductive options.
Last updated: 7/21/2017

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

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include carbamoyl-phosphate synthetase deficiency, argininosuccinic aciduria, hyperammonemia due to N-acetylglutamate synthase deficiency, citrullinemia type 1 and argininemia.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Ornithine transcarbamylase deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

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

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • Good Days provides help to patients with life-altering conditions. Assistance includes help with the cost of medications and travel.
  • The HealthWell Foundation provides financial assistance for underinsured patients living with chronic and life-altering conditions. They offer help with drug copayments, deductibles, and health insurance premiums for patients with specific diseases. The disease fund status can change over time, so you may need to check back if funds are not currently available.
  • The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Education Resources

  • The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

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

  • Genetics Home Reference (GHR) contains information on Ornithine transcarbamylase deficiency. This website is maintained by the National Library of Medicine.
  • 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.
  • 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

News

Other Conferences

  • Reaching for a Cure: 2011 NUCDF Annual Conference, July 8 2011 - July 10, 2011 
    Location: Sheraton Denver Downtown, Denver, Colorado
    Description: This conference offers the unique opportunity to meet other UCD families, stay informed, and learn about new advances in research, treatment and management to improve the lives of children and adults with UCD. Working together, our NUCDF families and community of committed researchers and medical professionals are making a major impact with advances in the understanding of UCDs, accelerating research, and improved outcomes in children and adults with UCD. In the past four years, research for UCDs has increased by 400%! Let's continue the momentum and end the devastating effects of UCD.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My son and daughter-in-law recently lost a baby boy to ornithine transcarbamylase (OTC) deficiency. My daughter-in-law has been identified as a carrier. Is it possible for carrier females to have a healthy baby? See answer


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