What is citrullinemia?

Citrullinemia is an inherited disorder that causes excess nitrogen, in the form of ammonia, and other toxic substances to build up in the blood. There are two types of citrullinemia. Citrullinemia type 1 (also known as classic citrullinemia) is the most severe form and usually becomes evident in the first few days of life. Citrullinemia type 2 appears later in childhood or during adulthood. This page focuses on citrullinemia type 1.

Causes

Citrullinemia type 1 is caused by mutations in the ASS1 gene, which is responsible for producing a particular enzyme that helps break down ammonia in the body. When this enzyme does not perform this function, ammonia accumulates and causes the symptoms of citrullinemia.

People with citrullinemia type 1 inherit one mutation from each of their parents, so that both copies of the gene in each cell have the mutation. Each parent has one mutation, which makes each parent a carrier.

Symptoms

Infants with citrullinemia type 1 may experience vomiting, lack of appetite and progressive lethargy, and they show signs of increased intracranial pressure. Affected infants may also experience seizures.

How is citrullinemia diagnosed?

Citrullinemia type 1 can be diagnosed through newborn screening programs. Molecular genetic testing for ASS1 gene mutations can confirm the diagnosis.

Treatment

Treatment for citrullinemia type 1 requires the coordinated efforts of a team of specialists, including metabolic specialists, neurologists and dieticians. Medications are necessary to remove excess ammonia from the body. Dialysis can also be used to remove ammonia from the blood in severe cases.

People with citrullinemia type 1 must follow dietary restrictions that limit the amount of protein to avoid the development of excess ammonia. Specialized dietary formulas and supplements can provide an infant with enough protein to ensure proper growth. A person with citrullinemia needs to remain on a low-protein diet for the rest of their life.

Affected individuals should be followed closely and have periodic blood tests to determine the level of ammonia in the blood.

Liver transplantation performed during infancy has the potential to improve quality of life and prolong survival in some patients with citrullinemia.  The healthy donor liver has normal levels of enzymes and pathways for processing nutrients, preventing the buildup of ammonia.