On the horizon: Efforts in urea cycle disorders to better predict severity and develop novel treatment strategies

Urea cycle disorders (UCD) result from either direct deficiency of a urea cycle enzyme or improper transport of urea cycle intermediates between cellular compartments. The urea cycle is the primary metabolic mechanism by which the body detoxifies waste nitrogen that otherwise accumulates as ammonia. Given this critical role, individuals with a UCD can present with severe hyperammonemia that may prove fatal. Furthermore, the care and management of those with a UCD is challenging and is hampered by our limited ability to prospectively predict the severity of disease in individuals based upon biochemical or molecular results. Similarly, treatment paradigms for UCD, while resulting in improvement in symptomatology are far from curative. Recent preclinical and clinical research has focused on both developing reliable predictors of severity and at advancing therapies and treatments that move closer to a cure. We present here an overview of this emerging work, targeting both areas of research, to provide a review of the state of investigation with regard to UCD.