Ornithine transcarbamylase (OTC) deficiency is a genetic, metabolic condition where there is a build-up of ammonia in the blood. Ammonia is produced during break down (metabolism) of protein, and can be toxic. The liver normally converts ammonia into urea, which is then excreted in urine; this process is called the urea cycle.

OTC deficiency is a urea-cycle disorder, caused by complete or partial lack of an urea cycle enzyme called ornithine transcarbamylase (OTC). When there is not enough OTC, excess ammonia builds up in the body, leading to hyperammonemia (excess ammonia in blood). Ammonia is a neurotoxin, and hyperammonemia can cause damage to the nervous system, leading to neurological symptoms, and can be life-threatening.

Symptoms and severity of OTC deficiency can vary widely between individuals. Individuals with partial deficiency in OTC often have milder symptoms, with symptoms developing later in life. Complete deficiency of OTC, which is more common in males, results in more severe symptoms that usually develop shortly after birth. Symptoms in babies may include rapid breathing, vomiting, extreme tiredness, and can progress to neurological symptoms such as seizures, low muscle tone, respiratory problems, encephalopathy (brain dysfunction) and coma.

Below on this page is some information about this condition as well as links to useful resources for Australians living with a rare disease.

Synonyms: OCTD, OCT deficiency, OTC deficiency, ornithine carbamoyltransferase deficiency, hyperammonemia due to ornithine transcarbamylase deficiency, deficiency of citrulline phosphorylase

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:664 Ornithine transcarbamylase deficiency

ICD-11: 5C50.AY Other specified of urea cycle metabolism

Rare diseases typically display a high level of symptom complexity. There is often a wide range of symptoms and the symptoms may vary between individuals in terms of its presentation, severity, duration and impact.

Please speak to your medical team to learn more about the symptoms of this condition

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

OTC deficiency is a genetic condition, caused by disease-causing genetic changes (variants) in the OTC gene on X chromosome (X-linked inheritance).

Both males and females can be affected. As males only have one X chromosome, they have one copy of the OTC gene, so if their OTC gene has the disease-causing genetic variant, they will have OTC deficiency. Females have two X chromosomes and two copies of OTC gene – if at least one of their copies has the disease-causing genetic variant, they may be affected; whilst most females will have no or mild symptoms, some females may be as severely affected as males.

These genetic variants can be passed on to the next generation. More information on X-linked inheritance pattern can be found at Centre for Genetics Education: X-linked inheritance. In some cases, these genetic variants can occur randomly before birth (de novo), and is not passed down from their parents.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

A timely diagnosis is critical for better patient outcomes, the provision of the best possible care and treatment options, access to services and support, increased reproductive confidence and the ability to participate in clinical trials.

Please speak to your medical team to learn more about the available diagnostic pathways for this condition.

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the treatment of OTC deficiency may include general practitioners (GP), paediatricians, geneticists, metabolic physicians, genetic counsellors, dietitians, nephrologists and others. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Metabolic Dietary Disorders Association (MDDA): Metabolic Clinics include a list of metabolic clinics in Australia that provide comprehensive diagnostic and management services for children and adults with inborn errors of metabolism.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. Palliative care is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. For more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

If you know of any relevant care guidelines, please let us know via the Contribute page.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

If you know of any relevant emergency management guidelines or information relevant to emergency care, please let us know via the Contribute page.

Metabolic Dietary Disorders Association (MDDA): Latest Research Updates has information about key areas of ongoing research for various inborn errors of metabolism conditions, including urea cycle disorders.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Australian Organisation:

Metabolic Dietary Disorders Association

Website: https://mdda.org.au/

Metabolic Dietary Disorders Association Inc (MDDA) are the national peak consumer body dedicated to supporting, educating, connecting, and representing all individuals their families and carers living with Inborn Errors of protein Metabolism (IEpM).

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

OTC deficiency varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

• The ASIEM Low Protein Handbook for Urea Cycle Disorders
• Fruit and Vegetables Counting Lists
• Protein Counting List

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information relevant to OTC deficiency can be found at:

• National Organization for Rare Disorders (NORD): Ornithine Transcarbamylase Deficiency
• Genetic and Rare Diseases (GARD) Information Center: Ornithine transcarbamylase deficiency
• The ASIEM Low Protein Handbook for Urea Cycle Disorder

StatPearls: Ornithine Transcarbamylase Deficiency

Online Mendelian Inheritance in Man, OMIM®: #311250 Ornithine transcarbamylase deficiency, Hyperammonemia due to

Orphanet: Ornithine transcarbamylase deficiency

Human Phenotype Ontology (HPO): Ornithine transcarbamylase deficiency

Inborn Errors of Metabolism Knowledgebase (IEMbase): #IEM0058 OTC-related Ornithine transcarbamylase deficiency

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team. If you would like to see more information added to this page, please reach out via the Contact form. If you would like to share relevant resources for this condition, please visit the Contribute page.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.