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Urea cycle defects (UCDs)

Summary of information

Urea cycle disorders (UCDs) comprise a group of inborn errors of metabolism affecting the detoxification of ammonia. The urea cycle consists of six consecutive enzymatic steps and in addition, two transporters are required for the urea cycle function. The urea cycle is present in the liver and is located in mitochondria as well as in the cytosol of only periportal hepatocytes. If any of these enzymes or transporters is defect, the main resulting medical problem is hyperammonemia which can be life-threatening. Besides the detoxification of ammonia, the synthesis of the amino acid arginine is another important function of the urea cycle.

The clinical phenotypes of patients affected by UCDs comprise a continuum ranging from early onset (i.e. neonatal during the first days of life) hyperammonemic crisis in severe defects to late onset of disease in less severely affected patients which can occur at any age (including late adulthood). If hyperammonemia develops, signs and symptoms are mainly neurological because ammonia is primarily toxic to the central nervous system; however, the clinical picture is unfortunately highly unspecific. Thus, to diagnose patients suffering from UCDs on their clinical presentation alone will be challenging. For this reason, ammonia must be determined immediately in any situation when a UCD is suspected.

If a UCD is suspected, a number of biochemical, enzymatic and genetic tools exist. To contact a specialist might be a good idea to plan the work-up most efficiently and least invasive. For some UCDs, biochemical tests alone can be sufficient to make the diagnosis. Others require either enzymatic or genetic tests. For reasons of family investigations and future pregnancies, mutation analysis should be considered in all affected patients.

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