Citrin Deficiency

Citrin deficiency (also known as citrullinemia type II) is an inherited disorder in which a protein called citrin does not work properly. This condition causes ammonia and other toxic substances to build up in the blood. One type of citrin deficiency appears shortly after birth with liver dysfunction, poor growth and low blood sugar. Symptoms are usually not severe and resolve after the first year of life; however, some infants develop chronic or fatal liver disease. Onset of the second type of citrin deficiency is usually in adolescence or adulthood and is associated with recurrent rising levels of ammonia in the blood, usually triggered by alcohol or sugar intake, certain kinds of medication or surgery. Symptoms may include behavior change, memory loss, seizure, coma, or death. For some, liver dysfunction is present as infants. Intellectual disabilities may develop in later stages or may be present in untreated individuals. Citrin deficiency may be managed by dietary treatment or liver transplantation. Long-term outcome can be excellent if appropriately managed. Citrin deficiency is caused by pathogenic variants in the SLC25A13 gene.

Citrin deficiency is inherited in autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for citrin deficiency. However, the risk to have a child affected with citrin deficiency is increased. Testing of reproductive partners is recommended for carriers of citrin deficiency.

Citrin deficiency is primarily found in East Asia, but has also been reported in other populations. In Japan, citrin deficiency is estimated to occur in 1 of in 17,000 newborns.

Genetics Home Reference: Citrullinemia (http://ghr.nlm.nih.gov/)
Genetic Alliance: Citrin Deficiency (http://www.diseaseinfosearch.org/)

OMIM [SLC25A13: 603859] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Citrin Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing