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Ornithine Transcarbamylase Deficiency (OTC)
Sunday, 15 August 2004
Sunday, 15 August 2004


Ornithine Transcarbamylase Deficiency (OTC) is a rare inherited disorder that affects the metabolism of nitrogen. Nitrogen comes from the protein found in our diet or from the breakdown of protein in our body that occurs when we are sick. Nitrogen from these sources is usually in the form of a chemical called ammonia. Ammonia must be removed from the body and for this to happen it must first be converted into another chemical called urea. The body converts ammonia to urea by a process called the urea cycle. The urea produced from this cycle will then be excreted by the kidneys in the urine. People with OTC and other urea cycle disorders cannot convert and excrete ammonia. When this happens, ammonia will build up in the body. This build up of ammonia is harmful because it is toxic to the body; especially the brain.


OTC is a very rare disease that mostly affects children. It is estimated that OTC occurs in approximately 1 out of every 80,000 births in the United States. Exactly how often this disease occurs is not known.

Signs and Symptoms

Signs and symptoms of OTC usually occur soon after birth, often with the first feeding. It is possible, however, for the first signs and symptoms not to appear until childhood or even adulthood. Some of the more common signs and symptoms are: 1. Abnormal drowsiness (lethargy) that may lead to coma 2. Persistent vomiting 3. Heavy or rapid breathing 4. Poor feeding, lack of appetite 5. Enlarged liver 6. Seizures 7. Decreased muscle tone 8. Low body temperature 9. Irritability 10. Loss of coordination 11. Disorientation or confusion

Possible Causes

OTC is a genetic disorder that affects one of the steps of the urea cycle. In OTC there is a deficiency of an enzyme called Ornithine Transcarbamylase (OTC). This enzyme’s role is to combine a molecule named ornithine with a molecule named carbamoyl phosphate to make cirtulline. This is the first step of the urea cycle. If this enzyme is missing or not working properly the urea cycle does not work correctly and ammonia builds up in the body. The gene that causes OTC has been identified and is on the X chromosome. Because this gene is located on the X chromosome it is inherited in an X-linked recessive manner. Males have one X chromosome and one Y chromosome. Females have two X chromosomes and no Y chromosome. Males with a copy of the OTC gene with a change (mutation) are more severely affected than females because females have a second X chromosome that partially, “protects” them. Females with a changed copy are called carriers because the have a changed copy of the gene but often have no or mild symptoms. A carrier female, even if she has no symptoms herself is at risk of passing the gene to her children.


When any urea cycle disorder is suspected, blood tests are done to measure the amount of ammonia in the body. Ammonia levels will be very high in patients with OTC deficiency while urea levels may be slightly low. Other blood tests may show abnormalities in blood electrolytes, amino acids and molecules like ornithine and carbamoyl phosphate. Urine and other tests may be done to look for other urea cycle disorders or other disease that cause high levels of ammonia. In OTC deficiency, there will also be a high level of orotic acid in the urine. The diagnosis of OTC is usually made by checking for OTC activity in liver cells. A biopsy is taken of the liver and analyzed to see if there is a deficiency of OTC. Patients with OTC will show very little OTC activity.


OTC is a chronic disease that must be managed over the patient’s lifetime. Long term follow-up with doctors and nutritionists familiar with this disease is very important. Ammonia levels must be closely monitored. The main goal of treatment is to control the level of ammonia and avoid any rapid rise in the level of ammonia associated with a viral or other illness. This strategy involves having a strict diet of small amounts of protein with a high number of calories. Medications can also be used to help the body get rid of the excess ammonia.


If OTC goes untreated, the disease can become very serious and even cause death. Mismanagement of the disease and episodes of high ammonia can also cause brain damage, coma and/or death. However, if the disease is treated from birth and all treatments are followed closely, the child can have a very good prognosis, living a life with almost no symptoms. While there is no cure for this disease, gene therapy is being researched to replace OTC in those people who have the deficiency. Education is important for families because of the possibility that females could be carriers of the gene that causes this disease.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


National Urea Cycle Disorders Foundation
A great site with detailed information about the disease, treatment options, support groups, and ongoing clinical research.

CLIMB (Children Living with Inherited Metabolic Diseases)
UK Organization dedicated to fighting metabolic diseases through research, awareness and support. This organization provides advice, information and support on all metabolic diseases to children, young adults, and families.

Contact a Family
Great website to contact other families with disabled children who suffer from rare diseases. This organization is a charity that helps families to cope with the burdens of caring for a child with a rare disease.

Save Babies Through Screening
A great website with information on OTCD and other urea cycle disorders, screening for the disorder as well as support for those affected. There are also links to other helpful websites.

Google Search for Ornithine Transcarbamylase Deficiency (OTC)

References and Sources

Emedicine.com: OTC deficiency www.emedicine.com/PED/topic2744.htm MedlinePlus: OTC deficiency www.nlm.nih.gov/medlineplus/ency/article/000372.htm OMIM: OTC deficiency www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=311250 National Organization of Rare Diseases: OTC deficiency www.rarediseasesnetwork.org/ucdc/otc.htm National Urea Cycle Disorders Foundation: OTC deficiency www.nucdf.org/