Urea cycle disorders are rare genetic disorders that occur when one of the six enzymes involved in removing ammonia from the blood is depleted. Symptoms range from irritability to coma and death, and treatment involves protein restriction and medication to remove ammonia. Liver transplants can serve as a cure for some cases.
A urea cycle disorder (UCD), also known as a urea cycle defect, is a rare genetic disorder that occurs when levels of one of the six enzymes involved in the removal of ammonia from the blood are depleted. Normally, the six enzymes of the urea cycle catalyze the steps required for the conversion of nitrogen to urea. The urea is then eliminated from the body in the urine. When there is a defect in one of these enzymes, ammonia builds up in the blood and causes toxicity. Treatment involves controlling the intake of nitrogenous compounds, such as proteins, and taking medications that help remove ammonia from the blood.
These disorders are rare congenital metabolic disorders involving the urea cycle. In the urea cycle, nitrogen, a byproduct of protein metabolism, is removed from the body through its conversion into urea. Also known as the ornithine cycle, nitrogen is first converted to ammonia and then to urea. There are six types of urea cycle disorders, named according to which enzyme is inadequate or totally absent. These types include N-acetylglutamate synthase deficiency, carbamoyl phosphate synthetase I deficiency, ornithine transcarbamylase deficiency, argininosuccinic acid synthetase (AS) deficiency or citrullinemia, argininosuccinase acid lyase (AL) deficiency or argininosuccinic aciduria, and arginine deficiency.
Symptoms of a urea cycle disorder depend on the severity of the deficiency and how early it is diagnosed. Some children are unable to survive beyond birth or infancy because they remain undiagnosed. An estimated 20% of sudden infant death syndrome (SIDS) cases may be due to an undiagnosed urea cycle disorder. A newborn with UCD may show symptoms of irritability, vomiting, lethargy, seizures, or hypotonia. If left unaddressed, the child eventually suffers breathing difficulties and coma, and often dies.
Children with mild to moderate UCD may show symptoms of hyperactivity, deviant behavior, self-inflicted injury, and a dislike of meat and other protein-containing foods. Progressive symptoms include vomiting, particularly after eating meat or other high-protein meals, delirium, and lethargy. These symptoms are caused by high levels of ammonia in the blood or hyperammonemia. It can be precipitated by events such as chicken pox or exhaustion. If left untreated, this condition eventually leads to coma and death.
Milder enzyme deficiencies occur among adult survivors. Adults with a urea cycle disorder typically experience episodes of symptoms that mirror stroke and can sometimes be delusional or lethargic. They are usually referred to a neurologist or psychiatrist due to changes in behavior. Without proper treatment, adults with UCD can suffer from permanent brain disease, coma, and death. Symptoms are often triggered by viral infections, childbirth, or by valproic acid, an anticonvulsant drug.
Treatment of any of the UCDs involves protein restriction that balances the individual’s need for essential amino acids and the body’s inability to remove ammonia. Amino acid formulas and vitamins and minerals, such as calcium, can be supplemented. Medications that help remove ammonia can be given through a nasogastric or gastrotomy tube. Ammonia levels are monitored through frequent blood tests. Hospitalizations are often required, and liver transplants have served as a cure for some urea cycle disorders.
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