Electrospray Ionization Mass Spectrometry of Transferrin: Use of Quadrupole Mass Analyzers for Congenital Disorders of Glycosylation.

Electrospray ionization (ESI) mass spectrometry of transferrin can be used to diagnose congenital disorders of glycosylation (CDG) by detecting abnormal -glycosylation due to reduced site occupancy or processing failure. Time-of-flight mass spectrometers are widely used to separate 25-45 charged ions in the / 1,700-3,000 range, and a summed zero-charge mass distribution is generated despite the risk of improper deconvolution. In this study, the low / region of the multiply-charged ion mass spectrum enabled a robust analysis of CDG. A triple quadrupole mass spectrometer, the standard instrument for newborn screening for inborn errors of metabolism, permitted the identification of the key ions characteristic of different types of CDG affecting , , , , and in the / 1,970-2,000 region. Charge deconvolution was used as a complementary tool for validating the findings. It was necessary to set a cutoff level for the evaluation, since small peaks indicating glycosylation failure or reduced sialylation were observed, even in control subjects. This method and workflow facilitates the implementation of MS-based analyses and the screening of CDG in clinical laboratories.