Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of
urea cycle metabolism, with pronounced
citrullinemia and orotic aciduria being characteristic biochemical features. To further investigate the role of plasma
orotic acid and its possible use for monitoring the metabolic status in ASD, we determined plasma
orotic acid,
amino acid, and
ammonium levels in plasma samples collected over a period of 3 years from a patient who is now 8 years of age.
Orotic acid plasma concentrations varied widely from less than 1 micromol/l to more than 60 micromol/l. The renal clearance of
orotic acid was eightfold the glomerular filtration rate, thus supporting an active mechanism underlying the excretion of this
pyrimidine. Data obtained during a metabolic crisis yielded a statistically significant linear correlation of
orotic acid plasma levels with those of
glutamine and
ammonium, which are generally accepted for assessment of the successful treatment of this disorder. Our data revealed no advantage of plasma
orotic acid concentrations over the established
amino acids (
glutamine and
arginine) and
ammonium for determining acute treatment responses. Since several effects of high levels of
orotic acid have been described in mammals, further research is necessary to assess a possible contribution of
orotic acid to the pathogenesis of ASD and the use of plasma
orotic acid levels in the long-term monitoring of these patients.