Hereditary Disorders of Purine and Pyrimidine Metabolism: Identification of Their Biochemical Phenotypes in the Clinical Laboratory

Abstract

To describe a laboratory approach to the diagnosis of hereditary diseases of purine and pyrimidine metabolism and emphasize clinical situations in which these disorders should be considered in the differential diagnosis. Disease-specific patterns were identified in random specimens of ultrafiltered urine by using gradient high-performance liquid chromatography with diode-array detection, and reference ranges were established for uric acid, hypoxanthine, xanthine, and uracil expressed per creatinine in random specimens of urine. 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. Biologic fluids were prepared by ultrafiltration after addition of 3-methyluridine as internal standard. We used specimens negative for screening of metabolic disorders to establish reference ranges. Disease-specific patterns were identified in specimens with purine and pyrimidine disorders and several urea cycle disorders characterized by increased production of pyrimidine. The approach described identified disease-specific patterns of purine and pyrimidine disorders 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."