Urea cycle disorders
Definition
Urea cycle disorders are inborn errors in metabolism that can lead to brain damage and death. They involve a deficiency in one of the enzymes required by the urea cycle that removes ammonia from the blood.
Description
Ammonia accumulates in toxic levels if the urea cycle does not convert nitrogen from protein metabolism into urea for excretion into the urine. A series of biochemical reactions are necessary to complete the urea cycle. When an enzyme is missing or deficient, the cycle is interrupted and nitrogen accumulates in the form of ammonia. It cannot be excreted from the body and enters the blood stream, damaging nervous tissues, including the brain.
Seizures, poor muscle tone, respiratory distress, and coma follow if an affected infant is not treated. Acute neonatal symptoms are most frequently seen in boys with ornithine transcarbamylase, or OTC, deficiency. Mental retardation and even death may follow. People with partial deficiencies may not discover the problem until childhood or adulthood. Children may avoid meat or other protein foods. As ammonia levels rise in the body, individuals begin to show lethargy and delirium. Left untreated they may suffer a coma or death.
Sometimes young people with urea cycle disorders, who go undiagnosed, begin to show behavioral and eating problems. Those with partial enzyme deficiencies may experience episodes of high ammonia levels in the blood. This can occur after suffering from viral illnesses including chicken pox, or after eating high-protein meals, or even after significant physical exertion.
The incidence of adults with urea cycle disorders is increasing. Recent evidence has indicated that some people have survived undiagnosed into adulthood. They can suffer stroke-like symptoms, lethargy, and delirium. Without proper diagnosis and treatment, adults are at risk for permanent brain damage, coma, and death. Symptoms can appear after giving birth or after contracting a virus, and some adults have shown deficiencies after using the medication valproic acid (an anti-epileptic drug). Adult onset is more common in women with OTC deficiency.
Different enzymes may be lacking in the various forms of urea cycle disorders. The six major disorders of the urea cycle include:
- CPS–Carbamyl Phosphate Synthetase
- NAGS–N-Acetylglutamate Synthetase
- OTC–Ornithine Transcarbamylase
- ASD–Argininosuccinic Acid Synthetase (Citrullinemia)
- ALD–Argininosuccinase Acid Lyase (Argininosuccinic Aciduria)
- AG–Arginase
Genetic profile
All of these disorders are inherited as autosomal recessive traits except for ornithine transcarbamylase (OTC) deficiency. It is inherited as an X-linked trait, from the mother.
