The urea cycle is the metabolic pathway by which waste nitrogen is converted to urea, which is then excreted in the urine. The cycle has several steps, each catalysed by a different enzyme. Urea cycle defects result when there is a deficiency of one of these enzymes:

• N-acetyl glutamate synthase (NAGS) deficiency
• Carbamyl phosphate synthase (CPS) deficiency
• Ornithine transcarbamylase (OTC) deficiency
• Citrullinaemia (Argininosuccinate synthase deficiency)
• Argininosuccinic aciduria (Argininosuccinate lyase deficiency)
• Hyperargininaemia (Arginase deficiency)

The most common of the urea cycle disorders is OTC deficiency. Disturbance of the urea cycle results in a rise in ammonia concentrations in the blood and brain with associated irritability, vomiting, drowsiness and coma. The disorders commonly present in the first month of life but symptoms may start at almost any age. Arginase deficiency mostly presents with a neurological disorder (spastic diplegia) and developmental delay.

Management aims to control ammonia concentrations and prevent episodes of decompensation, as these are potentially serious. General measures include a protein restricted diet, arginine supplementation (as this becomes an essential amino acid in these disorders with the exception of hyperargininaemia), and the use of alternate pathway medicines which help rid the body of excess nitrogen bypassing the urea cycle. During periods of infection, protein intake is stopped, and glucose is given either by mouth or intravenously.

Inheritance patterns
The mode of inheritance of all these disorders is autosomal recessive, except OTC deficiency which is an X-linked disorder. Female carriers of OTC deficiency may be at risk of developing symptoms themselves.

Prenatal diagnosis
Prenatal diagnosis is available for all the conditions.

Medical text written October 2001 by Dr M Champion. Last updated January 2006 by Dr M Champion, Consultant in Paediatric Metabolic Medicine, Evelina Children's Hospital, London, UK.

Further Online Resources
Medical texts in The Contact a Family Directory are designed to give a short, clear description of specific conditions and rare disorders. More extensive information on this condition can be found on a range of reliable, validated web sites and links to them are included in the CD-ROM version of this Directory. Further information on these resources can be found in our Medical Information on the Internet article.

As Urea Cycle Disorders are metabolic diseases, support and advice are also available from Climb (see entry Metabolic diseases).