Ornithine transcarbamylase deficiency

What causes ornithine transcarbamylase (OTC) deficiency?

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.

Last updated on 05-01-20

How is ornithine transcarbamylase (OTC) deficiency inherited?

OTC deficiency follows X-linked inheritance. 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.

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 on 05-01-20

What is ornithine transcarbamylase (OTC) 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.

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

Last updated on 05-01-20

If a woman is a carrier of ornithine transcarbamylase (OTC) deficiency, what are the chances that she will pass the condition onto her children?

Women with an OTC gene mutation have a 50% chance of transmitting the disease-causing mutation to each child; sons who inherit the mutation will be affected; daughters will have a range of possible symptoms. Additional information about risk assessment can be accessed by clicking here. We encourage you to discuss this information with your healthcare provider or a genetic professional.

Last updated on 05-01-20

Selected Full-Text Journal Articles

Free full text - Scaglia, et al. Ornithine transcarba

Last updated on 04-27-20

Free full text - Riudor, et al. Ornithine transcarbamylase

Riudor, et al. Partial Ornithine Transcarbamylase Deficiency. Pediatrics 2003;111:1123-1124.

Last updated on 04-27-20

Name: Metabolic Support UK 5 Hilliards Court Sandpiper Way
Chester Business Park
Chester, CH4 9QP, United Kingdom
Phone: 0845 241 2173 Toll Free: 0800 652 3181 Email: https://www.metabolicsupportuk.org/contact-us Url: https://www.metabolicsupportuk.org
Name: National Urea Cycle Disorders Foundation 75 South Grand Avenue
Pasadena, CA, 91105, United States
Phone: +1-626-578-0833 Toll Free: 800-38-NUDCF (386-8233) Email: info@nucdf.org Url: http://www.nucdf.org
Name: The Brí Foundation Email: http://www.thebrifoundation.com/contact-us.html Url: http://www.thebrifoundation.com/

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