Inherited defects of purine and pyrimidine metabolism: Laboratory methods for diagnosis

The diagnosis of the majority of the known inherited defects of purine and pyrimidine metabolism can be achieved by analysing urinary excretion profiles. A quantitative measurement of the urinary uric acid/creatinine ratio should be the first approach for purine defects. The general screening system involves separation of the bases and nucleosides by reversed-phase high-performance liquid chromatography and multiwavelength UV detection. The catabolic defects of pyrimidine degradation can be diagnosed by gas chromatography-mass spectrometry as used for organic acids, For the detection of adenylosuccinase deficiency, several simple but effective thin-layer chromatographic methods are available. Techniques such as liquid chromatography-mass spectrometry, direct nega-tive-ion fast-atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy give promising results, but are not yet being used on a large scale. Patients should keep to a simple diet and preferably be free of medication in order to allow a reliable interpretation of the analytical data.