HEREDITARY DISORDERS OF PURINE AND PYRIMIDINE METABOLISM - IDENTIFICATION OF THEIR BIOCHEMICAL PHENOTYPES IN THE CLINICAL LABORATORY

Objective: To describe a laboratory approach to the diagnosis of hered itary diseases of purine and pyrimidine metabolism and emphasize clini cal situations in which these disorders should be considered in the di fferential diagnosis. Design: Disease-specific patterns were identifie d in random specimens of ultrafiltered urine by using gradient high-pe rformance liquid chromatography with diode-array detection, and refere nce ranges mere established for uric acid, hypoxanthine, xanthine, and uracil expressed per creatinine in random specimens of urine. Materia l and Methods: Diagnostically significant purines and pyrimidines were separated with use of a Supelco LC-18-S nucleoside column eluted with 25 mmol/L ammonium acetate buffer and acetonitrile-methanol-water. Bi ologic fluids were prepared by ultrafiltration after addition of 3-met hyluridine as internal standard. We used specimens negative for screen ing of metabolic disorders to establish reference ranges. Results: Dis ease-specific patterns were identified in specimens with purine and py rimidine disorders and several urea cycle disorders characterized by i ncreased production of pyrimidine. Conclusion: The approach described identified disease-specific patterns of purine and pyrimidine disorder s and several urea cycle disorders. We suggest that testing for purine and pyrimidine disorders be done in specimens evaluated in metabolic laboratories for ''screening for inborn errors of metabolism.''