Congenital disorders of glycosylation (CDG) comprise a group of multi-system diseases with an extremely variable phenotype. Manifestations range from severe developmental delay and hypotonia with multiple organ system involvement beginning in infancy, to hypoglycemia and protein-losing enteropathy with normal development, or isolated failure to thrive. Type I CDG comprises those disorders in which there are defects that affect the biosynthesis of dolichol-linked oligosaccharides in the cytosol or the endoplasmic reticulum (ER), as well as defects involving the transfer of oligosaccharides onto nascent glycoproteins. Type II CDG comprises all defects of further trimming and elongation of N-linked oligosaccharides in the ER and Golgi.
Serum or plasma N-glycan profile can be used to identify most subtypes of CDG type II, combined type I and type II, and multiple glycosylation disorders, such as various types of COG complex deficiencies (Conservated Oligometric Golgi).
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N-Glycan chains are firstly released from SDS denaturated serum glycoproteins via PNGase F digestion, and then permethylated. The permethylated N-glycan are measured by matrix-assisted laser desorption/ionization time of light mass spectrometry (MALDI- TOF). The structure of the glycans can be further analyzed by MALDI-TOF/TOF.
Comparing to normal serum or plasma, the changes in the N-glycan structure monitored by MALDI profile are used to identify the associated congenital disorders of glycosylation (CDGs) in patients serum or plasma.