Urinary uracil concentrations are a useful guide to genetic disorders associated with neurological deficits and abnormal pyrimidine metabolism

Abstract Elevated urinary uracil concentrations are characteristic of genetic deficiencies of enzymes catalysing the first two steps of the pyrimidine degradative pathway (Van Gennip et al 1993), dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHP). DPD is rate limiting for the whole pathway. Homozygotes are detected by the raised levels of uracil and thymine in urine. The pyrimidine synthetic route shares a common intermediate. carbamoyl phosphate, with the urea cycle. In urea‐cycle disorders such as ornithine carbamoyltransferase (OCT) deficiency, orotic aciduria resulting from an increased flux through the pathway has been used to detect hemizygotes or carriers following a protein, or more recently, an allopurinol load (Sebesta et al 1994). This paper demonstrates that uracil may be an even more useful guide to OCT carrier status and compares urinary uracil with concentrations found in genetic pyrimidine defects associated with neurological deficits.