Open AccessAbnormal N ‐glycan fucosylation, galactosylation, and sialylation of IgG in adults with classical galactosemia, influence of dietary galactose intake
Author(s) -
Treacy Eileen P.,
Vencken Sebastian,
Bosch Annet M.,
Gautschi Matthias,
RubioGozalbo Estela,
Dawson Charlotte,
Nerney Darragh,
Colhoun Hugh Owen,
Shakerdi Loai,
Pastores Gregory M.,
O'Flaherty Roisin,
Saldova Radka
Publication year - 2021
Publication title -
jimd reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 25
ISSN - 2192-8312
DOI - 10.1002/jmd2.12237
Subject(s) - fucosylation , galactosemia , glycan , galactose , glycosylation , cohort , medicine , chemistry , endocrinology , biochemistry , glycoprotein
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.