Late Onset OTC Deficiency Fact Sheet
How does OTC happen?
OTC is a genetic condition that is passed down from either mom or dad. It is an X-linked condition meaning the genetic change or mutation is on the X chromosome. Men have one X chromosome and women have two.
Fathers who have the mutation will always pass it to their daughters since they only have one X chromosome to give. They will not pass it to their sons since they pass their Y chromosomes to boys. Mothers who have the mutation will pass it on to their sons and daughters 50% of the time.
Women with this condition are termed carriers. In classic OTC, women have variable symptoms due to X-linked inactivation. The cells in a woman’s body decide which X-chromosome to turn off or on. With a mild mutation, like that in late-onset OTC deficiency, we would not expect women to be affected. Though we avoid oral steroids.
What is OTC deficiency?
OTC (ornithine transcarbamylase) deficiency is a disorder of the urea cycle in which protein is not completely broken down, causing an elevation of ammonia which is toxic to the brain. Late onset OTC deficiency tends to be a more mild form of the disease as it does not present in infancy. Typically it presents with a significant illness, fasting and/or steroid use. Symptoms of an emergency include: lethargy or difficulty waking, vomiting, seizures, confusion or other abnormal behavior.
Emergency Care for OTC deficiency
Immediate treatment is necessary to reduce ammonia levels and avoid damaging the brain. An urgent Emergeny Room visit is needed to provide IV fluids with dextrose (sugar) and possibly medications to lower ammonia.
Many individuals with late onset OTC have no daily symptoms. Some do not like eating meat based proteins. Symptoms typically occur with elevated ammonia levels and include: nausea, headache, vomiting, and difficulty concentrating.
How do I know I’m affected?
Genetic testing is the first step. The mutation is located on the OTC gene. If a family variant is known, testing can be focused on that particular gene change. If not, the entire gene should be examined with sequencing and deletion/duplication studies. Your local genetics clinic can arrange testing. If positive for the gene change, other labs may be needed to decide if treatment is necessary.
Treatment for OTC deficiency
All diagnosed individuals should avoid oral or IV steroids (skin and topical preparations are usually fine) as they worsen the disease. All those diagnosed should also be aware of the Emergency Protocol.
Females with late onset OTC deficiency have not been found to require other treatment. Though women should speak to their genetics clinic if they are concerned that they have symptoms related to OTC.
Depending on lab results, males may need medication to lower ammonia levels (ammonia scavengers), citrulline supplementation to continue the urea cycle, and, at times, a low protein diet with help of a metabolic dietitian.
Information provided by the University of Utah Health Metabolic Clinic.