title: IgG N-Glycosylation Galactose Incorporation Ratios for the Monitoring of Classical Galactosaemia.
abstract: Classical galactosaemia (OMIM #230400) is a rare disorder of carbohydrate metabolism caused by deficiency of the galactose-1-phosphate uridyltransferase enzyme (EC 2.7.7.12). The cause of the long-term complications, including neurological, cognitive and fertility problems in females, remains poorly understood. The relatively small number of patients with galactosaemia and the lack of validated biomarkers pose a substantial challenge for determining prognosis and monitoring disease progression and responses to new therapies. We report an improved method of automated robotic hydrophilic interaction ultra-performance liquid chromatography N-glycan analysis for the measurement of IgG N-glycan galactose incorporation ratios applied to the monitoring of adult patients with classical galactosaemia. We analysed 40 affected adult patients and 81 matched healthy controls. Significant differences were noted between the G0/G1 and G0/G2 incorporation ratios between galactosaemia patients and controls (p < 0.001 and <0.01, respectively). Our data indicate that the use of IgG N-glycosylation galactose incorporation analysis may be now applicable for monitoring patient dietary compliance, determining prognosis and the evaluation of potential new therapies.
authors.affiliation: National Institute for Bioprocessing Research and Training (NIBRT), Glycoscience Group, Mount Merrion, Blackrock, Dublin University College, Dublin, Ireland.
authors.forename: Henning
authors.initials: H
authors.lastname: Stockmann
authors.affiliation: Department of Infectious Diseases, King's College London, Faculty of Life Sciences and Medicine, Guy's Hospital, London, UK.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Coss
authors.affiliation: Maastricht University Medical Centre, Minderbroedersberg 4, Maastricht, The Netherlands.
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.affiliation: National Centre for Inherited Metabolic Disorders, Childrens University Hospital, Dublin, Ireland.
authors.forename: Ina
authors.initials: I
authors.lastname: Knerr
authors.affiliation: Mater Misericordiae University Hospital, Eccles St, Dublin, Ireland.
authors.forename: Maria
authors.initials: M
authors.lastname: Fitzgibbon
authors.affiliation: University College Dublin Clinical Research Centre, Eccles St, Dublin, Ireland.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Maratha
authors.affiliation: Centre for Population Health Sciences, Medical School, Teviot Place, Edinburgh, EH8 9AG, Scotland.
authors.forename: James
authors.initials: J
authors.lastname: Wilson
authors.affiliation: National Institute for Bioprocessing Research and Training (NIBRT), Glycoscience Group, Mount Merrion, Blackrock, Dublin University College, Dublin, Ireland.
authors.forename: Pauline
authors.initials: P
authors.lastname: Rudd
authors.affiliation: Mater Misericordiae University Hospital, Eccles St, Dublin, Ireland. etreacy@mater.ie.|University College Dublin Clinical Research Centre, Eccles St, Dublin, Ireland. etreacy@mater.ie.|Trinity College, Dublin, Ireland. etreacy@mater.ie.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Treacy