Plasma N-Glycan Profiling by Mass Spectrometry for Congenital Disorders of Glycosylation Type II

Abstract

BACKGROUND:Determination of the genetic defect in patients with a congenital disorder of glycosylation (CDG) is challenging because of the wide clinical presentation, the large number of gene products involved, and the occurrence of secondary causes of underglycosylation. Transferrin isoelectric focusing has been the method of choice for CDG screening; however, improved methods are required for the molecular diagnosis of patients with CDG type II.

Oligosaccharide Analysis in Urine by MALDI-TOF Mass Spectrometry for the Diagnosis of Lysosomal Storage Diseases

“…FOS were permethylated because the permethylation protects the terminal sialic acid residue and stabilizes the FOS during sample preparation and analysis (8,9 ). Briefly, permethylation of oligosaccharides was performed as follows.…”

High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation

“…This can be obtained by mass spectrometric analysis of transferrin glycopeptides 16,17 or released plasma N-glycans. [18][19][20][21] These methods, however, are time-consuming and lack information on the loss of complete glycans, as required for CDG-I diagnostics.…”

Glycome as Biomarkers

“…This study also successfully addressed the challenge of differentiating CDG type II diseases from other diseases with secondary causes of underglycosylation. This method is now being successfully applied in clinical research (Guillard et al 2011). When the glycosylation of serum proteins isolated from the individuals with autosomal recessive cutis laxa (ARCL) type II was investigated, all affected individuals were found to show a CDG type II pattern, and the underlying ATP6V0A2 gene encoding the a2 subunit of the V-type H + -ATPase defect was identified in several patients with ARCL type II.…”