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

Eileen P Treacy*, Sebastian Vencken, Annet M Bosch, Matthias Gautschi, Estela Rubio-Gozalbo, Charlotte Dawson, Darragh Nerney, Hugh Owen Colhoun, Loai Shakerdi, Gregory M Pastores, Roisin O'Flaherty, Radka Saldova

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Classical galactosemia (CG) (OMIM #230400) is a rare disorder of carbohydrate metabolism, due to deficiency of galactose-1-phosphate uridyltransferase (EC 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.

Original languageEnglish
Pages (from-to)76-88
Number of pages13
JournalJIMD reports
Issue number1
Publication statusPublished - Sept 2021

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