Citrullinemia type I

Citrullinemia type I is caused by mutations in the ASS1 gene. This gene provides instructions for making an enzyme, argininosuccinate synthetase 1 (ASS1), which is responsible for helping breakdown ammonia in the body. Mutations in the ASS1 gene reduce the amount of ASS1 enzyme in the body, leading to increased levels of ammonia in the blood. Ammonia is especially toxic to the nervous system, and high levels can lead to permanent brain damage and neurological problems like seizures and poor coordination.

Citrullinemia can be diagnosed through newborn screening. Every state in the US offers newborn screening for this disorder. When a baby tests positive for citrullinemia on a newborn screen, the diagnosis needs to be confirmed through specific medical test. Genetic testing can help identify the gene mutation in the family.

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person's medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Citrullinemia type I is inherited in an autosomal recessive pattern, which means both copies of the gene in every cell have mutations. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this.

Affected people inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

With treatment, people with citrullinemia type 1 can have normal growth and development. However, episodes of high ammonia can cause brain and nerve damage that cannot be repaired. This type of brain damage can cause permanent learning and intellectual disabilities, as well as problems with muscle control and coordination.

Citrullinemia type 1 occurs equally in both males and females and in all ethnic groups. It has been estimated that about 1 in 44,300 to 1 in 200,000 individuals worldwide have citrullinemia type 1.

For infants and children with high levels of ammonia, medications are necessary to remove the excess ammonia from the blood. Dialysis can also be used to clear ammonia from the blood. For long-term treatment, people with citrullinemia type 1 are put on a special low-protein diet and are given medications and supplements that help keep their ammonia levels low. Infants are given a special low-protein formula instead of breast milk or regular formula. it is recommended that people with citrullinemia remain on this diet for the rest of their life. Citrullinemia can also be treated with a liver transplant which is usually done before one year of age.

The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.