Pin Me

A Guide To Citrullinemia

written by: bjlbyron•edited by: lrohner•updated: 6/27/2011

Citrullinemia is a serious inherited disorder that has two forms, each one of which causes build up of toxins in the blood. Both forms, however, feature different symptoms and are caused by mutations in different genes. Read on to learn about the genetic condition known as citrullinemia.

  • slide 1 of 3

    What Is Citrullinemia?

    Citrullinemia is an inherited disorder that presents in two forms: a type I form and a type II form. The type I form is more common than is the type II form, as about 1 in about 60,000 people worldwide have the type I form and about 1 in every 100,000-230,000 individuals suffer from the type II form. The type II form is particularly prevalent among Japanese individuals. Both forms are usually debilitating and are often life-threatening.

    Type I citrullinemia typically presents shortly after birth and is due to extreme build up of ammonia in the body. Common symptoms include vomiting, seizures, frequent sleeping and even losing consciousness. Infants who suffer from type I citrullinemia are at heightened risk of coma and death.

    In some sufferers, type I citrullinemia symptoms do not first present until late childhood or even adulthood. This later-presenting variant of type I citrullinemia is milder, but less common, than in the early onset variant of the condition. Those who first experience type I citrullinemia after infancy suffer from symptoms such as balance problems, severe headaches, vision problems, and extreme fatigue.

    Type II citrullinemia symptoms, which can first present in adulthood, affect the nervous system, can be life-threatening, and include memory loss, aberrant behavior, confusion, and even coma. Interestingly, these symptoms can be induced or exacerbated by certain drugs, bacterial infection, and even some surgical procedures. Like the type I form, the type II form is caused by excess ammonia in the blood.



  • slide 2 of 3

    What Is Known About The Genetic Causes of Type I and Type II Citrullinemia?

    Type I citrullinemia is caused by mutations in a gene that is known as ASS1. This gene encodes a protein, which is specifically the protein argininosuccinate synthase 1, that is necessary for carrying out one particular step of a cellular process referred to as the urea cycle. It is the function of the urea cycle to break down ammonia into urea, which is a substance that is much less toxic to the body than is ammonia. People who have mutations in both copies of their ASS1 gene either do not make argininosuccinate synthase 1 or make a defective variant of that protein. In either case, these individuals are therefore unable to properly break down ammonia, which leads to harmful build up of that substance in their bodies.

    Mutations in a second gene, which is referred to as SLC25A13, are causative of type II citrullinemia. The SLC25A13 gene encodes the protein citrin. Among other its other functions, citrin, like argininosuccinate synthase, is needed by cells to properly carry out the urea cycle. Mutations in the SLC25A13 gene therefore affect the synthesis of citrin (it is either not made or it is otherwise defective), which in turn leads to inefficiency in, or shutdown of, the urea cycle. Again, such defects in the urea cycle cause excess ammonia to accumulate in the body, which in turn leads to the manifestation of the symptoms described in the previous section.

    This article is only meant to provide some basic information regarding the genetic condition known as citrullinemia. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.

  • slide 3 of 3


    Genetics Home Reference, National Institutes of Health, ASS1:

    Genetics Home Reference, National Institutes of Health, SLC25A13:

    Genetics Home Reference, National Institutes of Health, Citrullinemia:

    J.G. Thoene, GeneReviews, University of Washington, Citrullinemia Type I: