On-line Abstract Book

Mass Spectrometry in the Detection and Diagnosis of CDG (Congenital Disorders of Glycosylation)

Yoshinao Wada¹

Correspondence address: Yoshinao Wada, Osaka MCHRI / Osaka University, Molecular Medicine / Graduate School of Medicine, 840 Murodo-cho, Izumi, Osaka, 594-1101 Japan.

Web site: http://www.med.osaka-u.ac.jp/pub/inst-mch/

Keywords: Carbohydrates, Structure Determination; Glycoproteins; Glycosylation; Proteomic.

Congenital disorders of glycosylation (CDG) constitute a group of diseases affecting N-linked glycosylation pathways. The classical type of CDG, now called CDG-I, results from deficiencies in the early glycosylation pathway, in which 30-40 genes are involved, for biosynthesis of lipid-linked oligosaccharide and its transfer to proteins in endoplasmic reticulum. The CDG-II diseases are caused by defects in the subsequent glycoprotein N-glycan processing steps conducted by more than 50 gene products.

Mass spectrometry produced a milestone in CDG research, by localizing the CDG-I defect to the early glycosylation pathway in 1992.¹ Currently, detection of a drastic change, at a glycan-unit level, in the molecular mass of transferrin, either by electrospray ionization or matrix-assisted laser desorption/ionization, plays the central role in laboratory screening of CDG-I.² On the other hand, a sugar-unit or branch level of change is a typical phenotype manifesting CDG-II glycoproteins, and thus requires detailed analysis of the glycan structures for detection or diagnosis. This can be most probably achieved by a recently developed method of glycopeptide analysis by MS in a high throughput manner.³ In a broader point of view, the glycopeptide MS allows practical site-specific characterization of the oligosaccharide profiles of even highly heterogeneous glycoproteins,⁴ and will be a key interfacing technique in proteomics and functional/disease glycomics in the future.

1. Y. Wada et al., Biochem. Biophys. Res. Commun. 189, 832 (1992).
2. Y. Wada et al., Biol. Mass Spectrom. 23, 108 (1994).
3. Y. Wada et al., Anal. Chem. 76, 6560 (2004).
4. M. Tajiri et al., Glycobiology 15, 1332 (2005).