Serum transferrin carrying the xeno-tetrasaccharide NeuAc-Gal-GlcNAc2 is a biomarker of ALG1-CDG.
ALG1-CDG (formerly CDG-Ik) is a subtype of congenital disorders of glycosylation (CDG) where the genetic defect disrupts the synthesis of the lipid-linked oligosaccharide precursor required for N-glycosylation. The initial step in the investigation for these disorders involves the demonstration of hypoglycosylated serum transferrin (TF). There are no specific biomarkers of this CDG subtype known to date. An LC/MS approach was used to analyze sera from patients with ALG1-CDG, PMM2-CDG, suspected CDG, and individuals with alcohol abuse. We show mass spectrometric data combined with data from enzymatic digestions that suggest the presence of a tetrasaccharide consisting of two N-acetylglucosamines, one galactose, and one sialic acid, appearing on serum TF, is a biomarker of this particular CDG subtype. This is the first time analysis of serum TF can suggest a specific CDG type I subtype and we suggest this tetrasaccharide be used in the clinic to guide the ALG1-CDG diagnostic process.
Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Per
P
Bengtson
Human Genetics Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
Bobby G
BG
Ng
Centre for Metabolic Disease, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
Jaak
J
Jaeken
Centre for Human Genetics, KU Leuven, Leuven, Belgium.
Gert
G
Matthijs
Human Genetics Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
Hudson H
HH
Freeze
Department of Pediatrics, Clinical Sciences, Lund University, BMC D12, 221 84, Lund, Sweden. erik.eklund@med.lu.se.
Erik A
EA
Eklund
D000117:Acetylglucosamine / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008364:Mannosyltransferases / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D009844:Oligosaccharides / Q000378:metabolism*; D044967:Serum / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
D015415:Biomarkers; D009844:Oligosaccharides; D014168:Transferrin; D008364:Mannosyltransferases; C035777:chitobiosyldiphosphodolichol beta-mannosyltransferase; D000117:Acetylglucosamine