Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood.

These reactions process excess nitrogen, generated when protein is used for energy by the body, to make urea, which is excreted by the kidneys.

Affected infants typically appear normal at birth, but as ammonia builds up in the body, they develop a lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness.

Mutations in the ASS gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively.

Excess nitrogen, in the form of ammonia, and other byproducts of the urea cycle, accumulate in the bloodstream, leading to the characteristic features of type I citrullinemia.

[citation needed] Type II citrullinemia may also develop in people who had a liver disorder called neonatal cholestasis during infancy.

Researchers have found many infants with neonatal intrahepatic cholestasis have the same mutations in the SLC25A13 gene as adults with type II citrullinemia.