Urea Cycle Disease Overview:
In urea cycle disorders (UCD), the patient has a severe deficiency or is missing any of the first four enzymes (CPSI, OTC, ASS, ASL) in the urea cycle or the cofactor producer (NAGS) [Batshaw 1984, Summar 2001, Summar & Tuchman 2001]. Enzymes are proteins that are produced by living cells and regulate the body’s process to breakdown products, such as ammonia. Ammonia is a product of protein digestion and the urea cycle is required for the body to excrete ammonia. In patients with partial enzyme deficiencies, the first recognized clinical episode may be delayed for months or years. Early in life, infants with urea cycle disorders develop toxic levels of ammonia build-up in the blood.
Initial symptoms of hyperammonemia (too much ammonia in the blood) in the newborn are non-specific:
Symptoms may progress in the newborn that appears normal but rapidly develops cerebral edema (swelling of the brain). Symptoms of cerebral edema include the following:
Milder (or partial) urea cycle enzyme deficiencies can be triggered by illness or stress at almost any time of life resulting in multiple mild elevations ammonia in the blood. The first recognized clinical episode may be delayed for months or years. [Bourrier et al 1988] Hyperammonemic episode (too much ammonia in the blood) is marked by the following:
An elevated blood ammonia is a strong indication for the presence of a UCD. Amino acid analysis can be used to diagnose a specific urea cycle disorder. The amino acid arginine may be reduced in all urea cycle disorders, except arginase deficiency, in which it is elevated. A definitive diagnosis of CPSI deficiency, OTC deficiency, or NAGS deficiency is determined using the following:
The Urea Cycle Disorders Consortium (UCDC) is a part of NIH Rare Diseases Clinical Research Network (RDCRN). Funding and/or programmatic support for this project has been provided by the National Institute of Child Health and Human Development (NICHD) and the NIH Office of Rare Diseases Research (ORDR). Read Disclaimer >