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| Urea cylce disorder are genetic disorders caused by a deficiency in one of the enzymes in the urea cycle. The urea cycle involves a series of biochemical steps that take place in the liver, in which nitrogen is removed from the blood and converted to urea, which is then eliminated from the body in urine. Nitrogen is created in the body through the process of protein metabolism - when we eat protein, the body breaks it down to obtain amino acids that are used for growth and development of the cells. The waste product of this metabolism is nitrogen. There are six steps in the urea cycle, each of them involving a specific enzyme. Normally, urea is transferred into the urine and removed from the body, but when one of these urea cycle enzymes is missing or deficient, nitrogen accumulates and is converted to ammonia, a highly toxic substance, instead of urea. Ammonia reaches the brain through the blood where, at high levels, it can cause irreversible brain damage and/or death. There are six disorders of the urea cycle, each representing the deficient enzyme: |
| UREA CYCLE DISORDERS |
| Copyright 2002 National Urea Cycle Disorders Foundation |
| * Carbamyl Phosphate Synetase Deficiency - CPS * N-acetylglutamate Synetase Deficiency - NAGS * Ornithine Transcarbamylase Deficiency - OTCD * Argininosuccinate Synthethase Deficiency - ASD (also known as Citrullinemia) * Argininosuccinate Lyase Deficiency - AL or ASA (aslo known as argininosuccinic aciduria) * Arginase Deficiency - AG |
| All but one of the urea cycle disorders (OTCD) are transmitted as autosomal recessive genes, meaning that both the child's father and mother must pass a defiective gene to their affected child. Ornithine transcarbamylase deficiency is an X-linked trait, inherited in most cases from an unaffected mother, who is, often unknowingly, a carrier. There are also cases of OTCD being identified which were acquired through a mutation in sperm, and others that are not inherited, but accurred through a mutation in the fetus in utero. The symptoms of urea cycle disorders typically appear in either the neonatal period or in childhood. Children with severe urea cycle disorders usually show symptoms within the first few days of life. The baby may be irritable at first, followed by vomiting and increasing lethargy. Soon aftger, seizures, respiratory distress and coma may occur. If untreated, the child will die. These symptoms are caused by rising ammonia levels in the blood. Acute neonatal symptoms are most frequently seen in boys with OTC deficiency, but may also be seen in severe cases of the other disorders. Children with mild or moderate urea cycle enzyme deficiencies may not show symptoms until early childhood, or the symptoms may go unheeded. This childhood onset, called late-onset, can be seen in both boyus and girls. Symptoms include hyperactive behavior, sometimes accompanied by screaming and self-injurious behavior, agitation or irritability, and refusal to eat meat or other high protein foods. Later symptoms include vomiting, lethargy, delirium, seizures, and finally, if the conditionis undiagnosed and untreated, coma and death. Childhood episodes of high ammonia (hyperammonemia) may be brought on by viral illnesses, including chickenpox, or even exhaustion. The condition is often misdiagnosed as Reye's syndrome. Although rare, adults with a mild urea cycle enzyme ddeficiency have been identified who present with stroke-like symptoms, episodes of confusion, inability to concentrate, or lethargy. Adult-onset wymptoms have been observed following viral illnesses, childbirth, use of some drugs, and chemotherapy. Treatment for UCDs is individualized depending on the specific enzyme deficiency and the severity of symptoms. Basically, treatment consists of restriction of dietary protein, dietary supplementation with special formulas, and the use of medications which provide alternative pathsays for ammonia removal from the blood. Recent advancements in technologies such as tandem mass spectrometry have made it possible to screen all newborns for argininosuccinate synthetase defieiency (citrullinemia), argininosuccinate lyase, and arginase deficiency. Research into screens for OTC and CPS deficiencies has been initiated. We believe that comprehensive newborn screening will help prevent brain damage and other severe consequences of delayed diagnoses and save children's lives. For more information/support, please visit our webpage: National Urea Cycle Disorders Foundation |
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