Abnormal N -glycan fucosylation, galactosylation, and sialylation of IgG in adults with classical galactosemia, influence of dietary galactose intake.

Autor: Treacy EP; National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland.; Department of Paediatrics Trinity College Dublin Dublin Ireland.; UCD School of Medicine University College Dublin Dublin Ireland., Vencken S; Department of Medicine Trinity College Dublin Dublin Ireland., Bosch AM; Department of Pediatrics, Division of Metabolic Disorders Emma Children's Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands., Gautschi M; Department of Paediatrics and Institute of Clinical Chemistry Inselspital, University Hospital Bern Bern Switzerland., Rubio-Gozalbo E; Department of Pediatrics/Laboratory of Clinical Genetics Maastricht University Medical Centre Maastricht The Netherlands., Dawson C; Department of Endocrinology University Hospitals Birmingham NHS Foundation Trust Birmingham UK., Nerney D; National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland., Colhoun HO; NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training Dublin Ireland., Shakerdi L; National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland., Pastores GM; National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland., O'Flaherty R; NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training Dublin Ireland.; Department of Chemistry Maynooth University Kildare Ireland., Saldova R; NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training Dublin Ireland.; UCD School of Medicine, College of Health and Agricultural Sciences (CHAS), University College Dublin (UCD) Dublin Ireland.
Jazyk: angličtina
Zdroj: JIMD reports [JIMD Rep] 2021 Jul 22; Vol. 61 (1), pp. 76-88. Date of Electronic Publication: 2021 Jul 22 (Print Publication: 2021).
DOI: 10.1002/jmd2.12237
Abstrakt: Background: Classical galactosemia (CG) (OMIM #230400) is a rare disorder of carbohydrate metabolism, due to deficiency of galactose-1-phosphate uridyltransferase (EC 2.7.7.12). The pathophysiology of the long-term complications, mainly cognitive, neurological, and female infertility remains poorly understood.
Objectives: This study investigated (a) the association between specific IgG N -glycosylation biomarkers (glycan peaks and grouped traits) and CG patients (n = 95) identified from the GalNet Network, using hydrophilic interaction ultraperformance liquid chromatography and (b) a further analysis of a GALT c.563A-G/p.Gln188Arg homozygous cohort (n = 49) with correlation with glycan features with patient Full Scale Intelligence Quotient (FSIQ), and (c) with galactose intake.
Results: A very significant decrease in galactosylation and sialylation and an increase in core fucosylation was noted in CG patients vs controls ( P  < .005). Bisected glycans were decreased in the severe GALT c.563A-G/p.Gln188Arg homozygous cohort (n = 49) ( P  < .05). Logistic regression models incorporating IgG glycan traits distinguished CG patients from controls. Incremental dietary galactose intake correlated positively with FSIQ for the p.Gln188Arg homozygous CG cohort ( P  < .005) for a dietary galactose intake of 500 to 1000 mg/d. Significant improvements in profiles with increased galactose intake were noted for monosialylated, monogalactosylated, and monoantennary glycans.
Conclusion: These results suggest that N -glycosylation abnormalities persist in CG patients on dietary galactose restriction which may be modifiable to a degree by dietary galactose intake.
Competing Interests: The authors declared no potential conflict of interest. This study does not involve animals.
(© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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