The paucity of hyperammonemic crises together with spasticity, only seen in human
arginase I deficient patients and not in patients with other
urea cycle disorders, forces a search for candidates other than
ammonia to associate with the pathophysiology and symptomatology. Therefore, we determined
arginine together with some catabolites of
arginine in blood and cerebrospinal fluid of these patients as well as in extremely rare post-mortem brain material of two patients with
argininemia. The levels of
alpha-keto-delta-guanidinovaleric acid,
argininic acid and alpha-N-acetylarginine correlate with the
arginine levels in blood and cerebrospinal fluid of patients with imposed or spontaneous
protein restriction. The levels in blood are higher than the upper limit of normal in all studied patients. In addition to the highly increased levels of these same compounds in blood of a child with
argininemia, the increase of
guanidinoacetic acid, 24h before death, is remarkable. However, the manifest increases of these studied catabolites of
arginine are not seen in post-mortem brain material of the same pediatric patient. Otherwise a clear increase of
guanidinoacetic acid in post-mortem brain material of an adult patient was shown. A similar, comparable increase of
homoarginine in both studied post-mortem brain materials is observed. Therefore the study of the pathobiochemistry of
arginine in
argininemia must be completed in the future by the determination of the end catabolites of the
nitric oxide and
agmatine biosynthesis pathways in the knockouts as well as in the patients to evaluate their role, together with the here studied catabolites, as candidates for association with pathophysiology and symptomatology.