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Recent findings suggest that inborn errors of pyrimidine catabolism are less rare than generally assumed. We propose a complete set of diagnostic methods for these disorders, suitable for the clinical chemistry laboratory, and present relevant reference data. Applications of thin-layer chromatography, high-performance liquid chromatography, and conventional cation-exchange amino acid analysis lead to detection of various defects in pyrimidine degradation, including the recently described deficiencies of dihydropyrimidine dehydrogenase and dihydropyrimidinase. We also illustrate the potential of the methods to analyze for the catabolites expected to be increased in the urine of patients with ureidopropionase deficiency. Possible pitfalls in the diagnosis and ways to prevent misdiagnosis are demonstrated. The methods offer possibilities for clinical chemistry laboratories to extend their diagnostic capacity to the new area of pyrimidine degradation defects.

We describe a simple and rapid quantitative method for the simultaneous determination of 3,4-dihydroxyphenylalanine acid metabolites and 5-hydroxyindole-3-acetic acid. After solvent extraction from acidified urine, the acids are analyzed by reversed-phase high-performance liquid chromatography. For detection and quantification, we used a fluorescence detector in combination with an amperometric detector to obtain a high degree of specificity. Sample preparation and chromatographic analysis can be completed within an hour. Results by the method correlate well with those by a previously used gas-chromatographic method, but the new method is faster and avoids the need for derivatization.