Urea Cycle Disorder (UCD)

A urea cycle disorder (UCD) is an inherited disease that affects how the body removes the waste that is made from breaking down protein. Everyone needs protein, which is found in foods like dairy products, meat and fish. When a person eats food that contains protein, the body breaks it down into amino acids (the building blocks of protein that are used by the body for growth and tissue repair) and uses only what it needs. It changes the rest into nitrogen, which must then be removed by the body.

In a healthy person, the liver supplies several enzymes to change nitrogen into urea, which is then removed from the body in urine. This entire process is called the urea cycle.

The liver in a person with urea cycle disorder is missing an enzyme necessary to convert nitrogen into urea. As a result, ammonia, a highly toxic substance, builds up in the bloodstream and is not removed from the body. Untreated, the high amounts of ammonia can cause brain damage, coma and eventually death.

Urea cycle disorders are named based on the initials of the missing enzyme. They are:

  • OTC – ornithine transcarbamylase 
  • ASD – argininosuccinic acid synthetase (citrullinemia) 
  • AG – arginase 
  • ALD – argininosuccinase acid lyase (argininosuccinic aciduria) 
  • CPS – carbamoyl phosphate synthetase 
  • NAGS – N-acetylglutamate synthetase. 

Urea cycle disorders occur in about one in 30,000 newborns.

Urea cycle disorders are genetic.  Genes give the body instructions on how to break down protein.  We usually have two copies of each gene, and most UCD only occur when a person inherits a changed gene from both parents.  The exception is OTC deficiency, which is passed to the baby through the mother who is most often not affected. 

If both parents carry the defective gene, there is:

  • A 25 percent chance that their child will  develop the disorder 
  • A 50 percent chance that their child will receive one defective gene from one of the parents, which means the child will not show symptoms of the disorder; the child is a "carrier" 
  • A 25 percent chance their child will receive both working genes, one from each parent, and will be unaffected

With OTC deficiency, the risks that a person will be affected also depend if they are a boy or a girl.  If the mother carries the defective gene, there is:

  • A 50 percent chance that a male child will receive the defective gene from the mother, and therefore be affected
  • A 50 percent chance that a male child will receive the normal gene and be unaffected
  • A 50 percent chance that a female child will receive the abnormal gene, and be at risk of having symptoms related to OTC deficiency
  • A 50 percent chance that the female child will not receive the abnormal gene, and be unaffected

The age of onset and specific symptoms vary between the different types of UCD.  This disorder is most often diagnosed in infancy, but some children do not show symptoms until early childhood.  

In children with severe UCD, the symptoms will develop within the first 24 hours of life. While all of these symptoms may not be present, usually the baby will become very sleepy and irritable and will have feeding problems, including poor feeding and vomiting. Seizures, trouble breathing and coma may appear later.

Symptoms in children with mild or moderate UCD, who do not show symptoms until early childhood, may include:

  • Disliking meat or other foods rich in protein 
  • Vomiting, nausea 
  • Mental confusion or hyperactive behavior 
  • Tired often and / or hard to awaken 
  • Coma

The diagnosis is made by analysis of the urine and blood for abnormal metabolites (substance produced by metabolism), and high ammonia levels.

A liver biopsy can be done to confirm the diagnosis since it can show low levels of enzyme activity. Genetic tests also can be done to show whether there is a problem with one of the genes needed to break down proteins of the urea cycle to identify the particular type of urea cycle disorder.

An MRI or CT scan may be done to see if there is swelling of the brain caused by the ammonia in the blood.

Treatment is a lifelong process that doesn't cure the condition, but it can effectively manage the symptoms. Frequent blood tests are done to continue to monitor ammonia levels. Doctors in the areas of pediatrics, genetics and nutrition will work together to develop the child's treatment plan.

The child's treatment probably will involve: 

  • Low protein, high-calorie diet. Protein in the diet is lowered by avoiding protein-rich foods. Examples of foods that provide calories without loading the body with protein are fruits, vegetables and starches.
    However, protein is important for growth, so the protein restriction must be done with advice from a healthcare professional. A dietitian will plan and update a protein-restricted diet as the child grows. Some children need to take a special formula to make sure they are getting proper nutrition.
  • Medications. Some children will need to take medicine to help take extra ammonia out of the body. Oral medication is given that binds to ammonia and carries it out in the urine. 
  • Amino acid supplements. Depending on the type of UCD, amino acid supplements such as arginine or citrulline may be added to the diet to help give the body what it needs to make proteins that are important for growth and tissue repair, since children with urea cycle disorder can't make arginine on their own. 
  • Liver transplantation. Because the production of urea cycle enzymes takes place in the liver, a liver transplant can be an effective treatment for urea cycle disorder.

Your doctor will discuss the risks of transplantation with you and a decision must be made with the consideration of the pros and cons.

If a transplant is the best treatment option, the doctor and the other members of the patient care team will focus on preventing complications and will treat symptoms while your child waits for the donated liver.

Stresses on the body, such as illness, fever, surgery or an accident, can cause ammonia levels to rise. Care must be taken at these times, and extra calories will be needed to provide the stressed body with fuel.

Visits with your doctors and other specialists will be necessary to make adjustments to diet and medication. Having your child follow the diet your doctor gives is important for the child's health, growth and development.

There currently is no cure for urea cycle disorders. Outcomes depend on the type of urea cycle disorder, how severe it is, how early it is diagnosed and how closely the treatment plan and diet is followed.

Early diagnosis and treatment are required for the child to have a chance for good results. Babies who are diagnosed in the first week of life and are put on a diet right away may do well. If the child continues to carefully follow the diet, normal brain function can be reached.

If the child does not follow the diet or if the child has stress-induced symptoms, this can lead to repeated brain swelling and irreversible brain damage. Transplants have been effective in reversing the symptoms of urea cycle disorder.

Last Updated 06/2015