Ammonia accumulation in urea cycle defects (UCDs) leads to several cellular dysfunctions such as amino acid disturbances and disrupted neurotransmitter signaling (reviewed in Braissant et al, 2010, Mol Genet Metab 100 Suppl 1:S3-S12). Also, the pathophysiology of UCDs does not simply involve ammonia, and this is clinically supported by the fact that specific clinical features are seen in some UCDs and not others (such as hypertension in ASL deficiency, which could be cause by nitric oxide deficiency). Indeed, creatine synthesis in the brain can be altered by either an accumulation or deficiency of arginine (Brosnan et al, 2010, Mol Genet Metab 100 Suppl 1:S49-S52).

Philippe Campeau