Molecular Diagnosis of Congenital Disorders of Glycosylation

Abstract

Congenital disorder(s) of glycosylation (CDG) covers a wide range of disorders affecting glycoconjugates. A number of cases due to defects in the biosynthetic pathway of N-glycosylation have been identified in the last 30 years. MS has considerably helped to promote our knowledge of this emerging disease, by characterizing the molecular abnormalities of glycoproteins from the patients. ESI MS of transferrin detects a lack of N-glycans due to defects in the early glycosylation pathway in ER or allows profiling of glycoforms including immature structures derived from defects in the Golgi apparatus. MALDI MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. A preliminary result of CDG screening in Japan suggested an incidence of approximately one percent in 1,200 Japanese patients with developmental delay of unknown cause.