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
Affiliations
Eileen P. Treacy
National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland
Sebastian Vencken
Department of Medicine Trinity College Dublin Dublin Ireland
Annet M. Bosch
Department of Pediatrics, Division of Metabolic Disorders Emma Children's Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands
Matthias Gautschi
Department of Paediatrics and Institute of Clinical Chemistry Inselspital, University Hospital Bern Bern Switzerland
Estela Rubio‐Gozalbo
Department of Pediatrics/Laboratory of Clinical Genetics Maastricht University Medical Centre Maastricht The Netherlands
Charlotte Dawson
Department of Endocrinology University Hospitals Birmingham NHS Foundation Trust Birmingham UK
Darragh Nerney
National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland
Hugh Owen Colhoun
NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training Dublin Ireland
Loai Shakerdi
National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland
Gregory M. Pastores
National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland
Roisin O'Flaherty
NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training Dublin Ireland
Radka Saldova
NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training Dublin Ireland
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.
