Classical galactosaemia: novel insights in IgG N-glycosylation and N-glycan biosynthesis

Classical galactosaemia (OMIM #230400), a rare disorder of carbohydrate metabolism, is caused by a deficient activity of galactose-1-phosphate uridyltransferase (EC 2.7.7.12). The pathophysiology of the long-term complications, mainly cognitive, neurological and female fertility problems remains poo...

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Published in:European journal of human genetics : EJHG 2016-07, Vol.24 (7), p.976-984
Main Authors: Maratha, Ashwini, Stockmann, Henning, Coss, Karen P, Estela Rubio-Gozalbo, M, Knerr, Ina, Fitzgibbon, Maria, McVeigh, Terri P, Foley, Patricia, Moss, Catherine, Colhoun, Hugh-Owen, van Erven, Britt, Stephens, Kelly, Doran, Peter, Rudd, Pauline, Treacy, Eileen
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biomarkers
Biomarkers - blood
Case-Control Studies
Female
Galactosemias - blood
Galactosemias - genetics
Galactosemias - pathology
Glycosylation
Humans
Immunoglobulin G - blood
Immunoglobulin G - metabolism
Male
Mannosyltransferases - genetics
Mannosyltransferases - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
Monocytes - metabolism
N-Acetylglucosaminyltransferases - genetics
N-Acetylglucosaminyltransferases - metabolism
Polysaccharides - biosynthesis
Protein Processing, Post-Translational
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Summary:Classical galactosaemia (OMIM #230400), a rare disorder of carbohydrate metabolism, is caused by a deficient activity of galactose-1-phosphate uridyltransferase (EC 2.7.7.12). The pathophysiology of the long-term complications, mainly cognitive, neurological and female fertility problems remains poorly understood. The lack of validated biomarkers to determine prognosis, monitor disease progression and responses to new therapies, pose a huge challenge. We report the detailed analysis of an automated robotic hydrophilic interaction ultra-performance liquid chromatography N-glycan analytical method of high glycan peak resolution applied to serum IgG. This has revealed specific N-glycan processing defects observed in 40 adult galactosaemia patients (adults and adolescents), in comparison with 81 matched healthy controls. We have identified a significant increase in core fucosylated neutral glycans (P
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2015.254