Urea Cycle Disorder

A urea cycle disorder (UCD) is an inherited disease caused by the lack of an enzyme needed to break down ammonia in the body. Ammonia is a waste product that must be removed by the body.

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 ammonia, which must then be removed by the body.

In a healthy person, the liver supplies six enzymes to break down the ammonia into urea, which is then removed from the body in urine. This entire process is called the urea cycle and it occurs in liver cells.

The liver in a person with urea cycle disorder is missing an enzyme necessary to convert ammonia 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.

These 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 – Carbamyl phosphate synthetase
  • NAGS – N-acetylglutamate synthetase

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

Most urea cycle disorders are caused by a lack of a specific enzyme in the urea cycle. Urea cycle disorders are genetic, and most appear only if a person inherits a defective gene from both parents. If both parents carry the defective gene, there is a:

  • 25% chance that their child will develop the disorder
  • 50% 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”
  • 25% chance their child will receive both normal genes, one from each parent, and will be unaffected

However, this is not the case for ornithine transcarbamylase (OTC), which is the most common urea cycle disorder. It is passed to the baby through the DNA of the mother, and while girls or boys can inherit this genetic material, it is more commonly found in boys.

This disorder is often diagnosed in infancy, but some children do not show symptoms until early childhood. In infants, 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 vomit often. Seizures, breathing difficulty 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 difficult to awaken
  • Coma

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 health care professional. A dietitian will plan and update a protein-restricted diet as the child grows.
  • 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 citrullline 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 if advanced liver disease has developed. 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. Careful 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.