Abnormal -glycan fucosylation, galactosylation, and sialylation of IgG in adults with classical galactosemia, influence of dietary galactose intake.
Author
Treacy, Eileen PVencken, Sebastian
Bosch, Annet M
Gautschi, Matthias
Rubio-Gozalbo, Estela
Dawson, Charlotte
Nerney, Darragh
Colhoun, Hugh Owen
Shakerdi, Loai
Pastores, Gregory M
O'Flaherty, Roisin
Saldova, Radka
Publication date
2021-07-22Subject
Diseases & disorders of systemic, metabolic or environmental originGenetics
Paediatrics
Gastroenterology
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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.Citation
Treacy EP, Vencken S, Bosch AM, Gautschi M, Rubio-Gozalbo E, Dawson C, Nerney D, Colhoun HO, Shakerdi L, Pastores GM, O'Flaherty R, Saldova R. Abnormal N-glycan fucosylation, galactosylation, and sialylation of IgG in adults with classical galactosemia, influence of dietary galactose intake. JIMD Rep. 2021 Jul 22;61(1):76-88. doi: 10.1002/jmd2.12237Type
ArticleAdditional Links
https://onlinelibrary.wiley.com/journal/21928312PMID
34485021Journal
JIMD ReportsPublisher
Wileyae974a485f413a2113503eed53cd6c53
10.1002/jmd2.12237