Simplified screening for organic acidemia using GC/MS and dried urine filter paper: a study on neonatal mass screening.

Abstract

A simplified method for organic acidemia screening using GC/MS, the urease/direct method, is now available. To establish a practical screening system for organic acidemias, we studied the usefulness of dried urine filter paper (filter paper urine) and the application of a personal computer-based system of automated metabolic profiling and interpretation (automated system) that we earlier developed. In a comparison of filter paper urine with liquid urine, creatinine levels ranging from 4.6 to 122.5 mg/dl, showed an excellent correlation (r=0.9554), when the volumes of blotted urine and distilled water soaked were the same. Recovery of all 17 compounds except for citrate was similar between liquid and filter paper urine. CV values of 22 compounds tested ranged from 5.5 to 22.4% in the liquid urine, and from 7.7 to 29.8% in the filter paper urine. The CV values in stable isotope dilution analysis were much smaller in all nine compounds tested. As to the stability of compounds, the percentage changes to values at day 0 were within about +/-25% on day 28. We compiled GC/MS data, including methylene unit values, quantifying and confirming ions of 163 different organic acids and others, to use the automated system. We analyzed specimens from 55 patients with 17 different metabolic disorders. In 54 of the 55 specimens, the correct diagnosis was successfully indicated. Neonatal mass screening for organic acidemias warrants ongoing attention using this simplified method and filter paper urine.