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