Urea cycle disorders revisited – clinical, biochemical and therapeutical aspects

Urea cycle disorders (UCDs) are inherited defects of nitrogen metabolism that can result in life-threatening hyperammonemia and severe neurological disease [1]. The overall incidence of the entire group of disorders is estimated at about 1 in 35.000 to 40.000 [2, 3] but there may still be underreporting due to undiagnosed patients. The affected pathway, the urea cycle, is only expressed in the liver and is the main route for detoxification of ammonia in the human body [4]. There are six enzymes and two transporters directly involved in this pathway but, in addition, several inherited and acquired conditions can lead to impaired urea cycle function. Accordingly, there is a long list of differential diagnoses that can result in primary or secondary hyperammonemia, i.e. direct or indirect defects of the urea cycle [5]. UCDs are panethnic diseases but the distribution of disorders around the world is heterogeneous resulting in different frequencies of single UCDs in Japan, Europe or the US. 