Screening for Pyrimidine Metabolism Disorders Using Dried Filter-Paper Urine Samples: Method Development and a Pilot Study in Nagoya City, Japan

A screening system for pyrimidine metabolism disorders by measurement with high-performance liquid chromatography using dried filter-paper urine samples is presented. This system permits the simultaneous determination of dihydrouracil, uracil, orotic acid and pseudouridine. The coefficient of variations for the four compounds on the filter-paper urine samples were 0.010∼0.069 and the recoveries were 98.5∼107.1%. The detection limits of the four compounds were 2∼20 μmol/liter. The correlation between the filter-paper urine samples and liquid urine samples was excellent (0.938-0.988). We supeculated that this method could be used to detect pyrimidine metabolism disorders, such as dihydropyrimidinuria, dihydropyrimidine dehydrogenase deficiency and hereditary orotic aciduria. As a pilot study, we have analyzed dried filter-paper urine samples from 34 200 healthy Japanese, and found three cases of dihydropyrimidinuria without clinical symptoms.