Ornithine Transcarbamylase Deficiency

What is ornithine transcarbamylase deficiency? 

Ornithine transcarbamylase deficiency is a genetic disorder that is characterized by an accumulation of ammonia in the blood. When ammonia levels are too high, it becomes toxic and especially impacts the nervous system, along with the liver.

There are multiple forms of this condition which are defined by the age of onset. The neonatal-onset form is very severe and occurs early in life, whereas the late-onset form does not appear until adolescence or adulthood and is less severe. 

What are the symptoms of ornithine transcarbamylase deficiency?

In the neonatal-onset form, symptoms appear soon after birth. The first effects include vomiting, refusal to eat, poor sucking, irritability, and lethargy. Respiratory abnormalities, seizures, an enlarged liver, and poor muscle tone soon follow. Without immediate treatment, children could slip into a coma, develop cerebral palsy, experience developmental delays, and develop intellectual disabilities. Treatment is extremely important, as this condition can be fatal without it. 

Symptoms of the late-onset form of ornithine transcarbamylase deficiency occur in episodes, often brought on by another illness. Symptoms during an episode include vomiting, irritability, lethargy, self-mutilation (such as biting), confusion, hyperactivity, and ataxia. During an episode, treatment is just as necessary as in the neonatal-onset form. Without it, there could be fatalities. 

What causes ornithine transcarbamylase deficiency?

A mutated OTC gene is responsible for this condition, and it is responsible for the ornithine transcarbamylase enzyme. This enzyme is necessary for the urea cycle, and when it is mutated, the cycle cannot run smoothly, resulting in an accumulation of ammonia. 

It is an X-linked disorder, so it impacts males more often than females. If females do have this condition, it is often less severe.

How is ornithine transcarbamylase deficiency diagnosed?

A diagnosis is made after noticing the characteristic symptoms. To confirm a diagnosis, doctors will perform blood tests, biopsies, and genetic testing. 

What are the treatments for ornithine transcarbamylase deficiency?

A team of specialists are often needed to best treat this condition. The goal of treatment is to reduce levels of ammonia in the blood and lower levels during an episode. Hospitalization may be necessary during an episode, too. Long-term treatment consists of dietary restrictions and alternative pathways therapy. The drugs Buphenyl, Ravicti, and Ammonul have been approved for ornithine transcarbamylase deficiency as well. 

Monitoring of the blood is heavily suggested to ensure that ammonia levels do not get too high. While a liver transplant can cure this condition, it is a very risky procedure and can cause complications. 

Symptomatic treatment is also used, such as occupational, language, speech, and physical therapy. 

Where can I find out more about ornithine transcarbamylase deficiency?

• • • U.S. National Library of Medicine
    • NORD
    • NIH