Treacy, Eileen P and Vencken, Sebastian and Bosch, Annet M and Gautschi, Matthias and Rubio-Gozalbo, M. Estela and Dawson, Charlotte and Nerney, Darragh and Colhoun, Hugh Owen and Shakerdi, Laoi and Pastores, Gregory M and O'Flaherty, Roisin and Saldova, Radka (2021) Abnormal N-glycan fucosylation, galactosylation, and sialylation of IgG in adults with classical galactosemia, influence of dietary galactose intake. Journal of Inherited Metabolic Disease, 61. pp. 76-88. ISSN 1573-2665

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Abstract

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.

Item Type:	Article
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.
Keywords:	biomarkers; classical galactosemia; dietary galactose; immunoglobulin G; N-glycosylation;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	15051
Identification Number:	https://doi.org/10.1002/jmd2.12237
Depositing User:	Roisin O'Flaherty
Date Deposited:	22 Nov 2021 15:47
Journal or Publication Title:	Journal of Inherited Metabolic Disease
Publisher:	Wiley Open Access
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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