What is Citrullinemia?

Citrullinemia is a rare genetic condition, most common in people of Japanese descent, where the urea cycle is interrupted and the body has trouble processing nitrogen, causing ammonia and other compounds to build up in the blood. This condition is one among a family of urea cycle disorders, genetic diseases where the liver's ability to metabolize nitrogen is compromised by enzyme deficiencies, and it can vary in degree of severity. Some people are diagnosed in childhood, while other cases may be identified later in life.

This condition is a recessive trait and someone needs to inherit two copies of the defective gene involved for citrullinemia to be expressed. In these patients, the body is deficient in the enzyme argininosuccinate synthetase. Type I citrullinemia usually onsets shortly after birth. The patient will experience seizures, vomiting, and loss of consciousness caused by extremely high levels of ammonia in the blood. Some people have a more mild form that onsets later. Morbidity and mortality from Type I cases can be very high.

In type II citrullinemia, the patient experiences neurological symptoms like behavioral changes and tremors, caused by damage to the nerves. This often appears in adolescence or adulthood, and it is less severe. It is also the less common form of the condition. People may be aware of the risks of adult onset if their parents have citrullinemia or the family in general is known to carry the disease, and may be monitored to catch the disease early.

Immediate treatment for citrullinemia when it is identified involves restriction of dietary protein and the intravenous administration of drugs like arginine and sodium phenylbutyrate to provide an alternate route for nitrogen metabolism and clear the blood. When the patient is stabilized, a nutritionist can work with the patient on developing a citrullinemia diet to reduce the load on the metabolism, and oral sodium phenylbutyrate and arginine will be used to help the patient metabolize nitrogen more effectively.

People with a family history of this condition could be carriers, and may want to discuss the disease with a genetic counselor if they are preparing to have children. The counselor can provide advice to help the patient make decisions about reproduction. Genetic counselors can also be involved in the diagnosis and evaluation of people with citrullinemia, to determine the severity of the condition and develop an appropriate treatment plan. They may be consulted for follow-up testing as a patient undergoes treatment to see how well the patient is responding.