Detection of Genetic Disorders of Glycosylation by Mass Spectrometry

Congenital disorders of glycosylation (CDG) form a group of autosomal recessive metabolic disorders arising from defects occurring during the biosynthesis of protein glycans. There have been extensive studies into N-linked glycan disorders in which transferrins are glycosylated to different degrees. There have been far fewer studies on the O-linked disorders which predominantly involve errors in glycosaminoglycan synthesis. In humans, the most common mucin O-glycosylation occurs in which an N-acetylgalactosamine is attached to the hydroxyl of either a serine or threonine and a single galactose is linked to this primary sugar. N-acetylneuraminic acid (NeuAc) attaches to the galactose to give either the asialo-, monosialoor disialoforms or asialoin the absence of NeuAc.