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Tuesday, 27 January 2004
Sunday, 28 November 2004


Citrullinemia is a rare inherited disorder caused by a missing or poorly functioning enzyme, named argininosuccinate synthetase. Children affected with this disorder are unable to process protein properly, and may experience vomiting, refusal to eat, abnormal drowsiness, and coma. This disorder is called citrullinemia because one of the products that build up in the body is called citrulline. A high level of citrulline in the blood is called citrullinemia.


This disease is not well studied and how often it occurs is not known at this time. Citrullinemia is found in many ethnic groups, and males and females are equally affected. Citrullinemia is a genetic disease inherited as an autosomal recessive trait. A child receives two copies of every gene, one from each parent. In order for a child to be affected by citrullinemia, that child must inherit two copies of the altered gene associated with citrullinemia, one from each parent. Even though each parent carries the gene for this disease, they are not affected by this disease because they each have a second, normal copy of the gene. When both parents have one normal gene and one altered gene, each of their children have a 25% chance of receiving two altered copies, which results in disease. This inheritance pattern is known in genetics as “autosomal recessive”.

Signs and Symptoms

While children affected by this disease most commonly show signs and symptoms soon after birth, some do not have any problems until they are much older. When infants become sick in the newborn period they often are very sleepy and difficult to wake up. They also feed very poorly and may vomit frequently. Older children, who are not affected soon after birth, are often diagnosed when they do not reach their developmental milestones on time. Other signs and symptoms include; irritability, heavy or rapid breathing, confusion, changes in personality, coma, poor growth, large liver, poor coordination, low muscle tone, and seizures.

Possible Causes

The enzyme involved, argininosuccinate synthetase, is part of the urea cycle. The job of the urea cycle is to break down and remove waste products from the body. The urea cycle changes ammonia, produced from the digestion of protein, into urea which is removed from the body through the urine. When this process does not work correctly, ammonia which is toxic builds up in the body. The high levels of ammonia cause the symptoms of the disease.


The diagnosis of citrullinemia is made in newborn babies who have poor feeding, irritability and low muscle tone. A high level of ammonia is found in the blood. Older children have developmental delay and when they are sick with colds or other illness they become very tired, vomit a great deal, and have changes in their personality which is also associated with a high level of ammonia in their blood. When children are sick, the main laboratory test is measurement of ammonia in the blood. Specialized tests include measurement of the levels of amino acids in the blood; this shows high levels of citrulline and other related amino acids. Urine can also be tested for organic acids. The diagnosis is confirmed by measuring the level of the enzyme in skin fibroblasts. This test requires a small piece of skin to be removed and tested.


There currently is no cure for this disease but treatment is available and can make a big difference in the lives of these children. The main focus of treatment is a high calorie diet that is low in protein. Certain amino acids need to be supplemented and some medications are available to help the body get rid of ammonia. When children are very sick, dialysis may be necessary to lower the very high levels of ammonia quickly. This can be stopped when they recover from their episode and resume their low-protein diet.


Prognosis is mainly dependent on how much damage had already been done when the child was first diagnosed, and on how well the level of ammonia can be controlled after that. High levels of ammonia are toxic to the nervous system and particularly the brain. Infectious diseases, such as colds and flu, can be very serious and even life threatening in these children. Even with the best care some children’s level of ammonia is very hard to control. Treatment, however, is becoming better and people with this disease are living longer and having happy and successful lives.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


C Kids
This site is run by a family with a daughter affected by a urea cycle disorder. It has links to other information and a discussion board for families dealing with this disorder.

National Urea Cycle Disorders Foundation
The mission of this site is to link families, friends and professionals who are dedicated to the identification, treatment and cure of urea cycle disorders.

Google Search for Citrullinemia

References and Sources

Tomomasa T (2001) Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy. J Pediatrics. 01 May 138(5):741-3 Lee B (2001). Long-term correction of urea cycle disorders. J Pediatrics. 01 Jan 138(1 Suppl) S62-71 Summar M (2001) Proceedings of a consensus conference for the management of patients with urea cycle disorders. J Pediatrics. 01 Jan 138(1 Suppl): S6-10 Consensus statement from a conference for the management of patients with urea cycle disorders. Urea Cycle Disorders Conference group. - J Pediatr - 01-JAN-2001; 138(1 Suppl): S1-5 Batshaw ML (2001). Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatrics 01 Jan 138(1 Suppl) S46-54, discussion S54-55. Leonard JV (2001). The nutritional management of urea cycle disorders. J Pediatrics. 01 Jan 138(1 Suppl) S40-44, discussion S44-45.