MALDI-TOF MS applied to apoC-III glycoforms of patients with congenital disorders affecting O-glycosylation. Comparison with two-dimensional electrophoresis.

Purpose: The O-glycan abnormalities accompanying some congenital disorders of glycosylation, namely conserved oligomeric Golgi-congenital disorders of glycosylation (COG-CDGs) and ATP6V0A2-CDGs, are mainly detected using electrophoresis methods applied to circulating apolipoprotein C-III. The objective of this study was to evaluate the reliability of MALDI-TOF MS of apoC-III for the detection and characterization of CDG-associated O-glycan defects.

Experimental Design: plasmas from CDG-negative, COG-CDG, and ATP6V0A2-CDG patients were analyzed and results were compared to those obtained using 2DE followed by Western blot.

Results: MALDI-TOF of apoC-III allowed to detect various significant O-glycan abnormalities in CDG-patients with emphasis to COG-CDG. Furthermore, in CDG samples, comparison study between 2DE and MALDI-TOF showed a particular behavior of monosialylated apoC-III in the mass spectrometer that could be related to an abnormal O-glycan structure.

Conclusions And Clinical Relevance: MALDI-TOF MS appears as a powerful technique for the analysis of apoC-III glycoforms for potential routine screening of COG- and ATP6V0A2-CDGs.