title: N-glycan abnormalities in children with galactosemia.
abstract: Galactose intoxication and over-restriction in galactosemia may affect glycosylation pathways and cause multisystem effects. In this study, we describe an applied hydrophilic interaction chromatography ultra-performance liquid chromatography high-throughput method to analyze whole serum and extracted IgG N-glycans with measurement of agalactosylated (G0), monogalactosylated (G1), and digalactosylated (G2) structures as a quantitative measure of galactose incorporation. This was applied to nine children with severe galactosemia (genotype Q188R/Q188R) and one child with a milder variant (genotype S135L/S135L). The profiles were also compared with those obtained from three age-matched children with PMM2-CDG (congenital disorder of glycosylation type Ia) and nine pediatric control samples. We have observed that severe N-glycan assembly defects correct in the neonate following dietary restriction of galactose. However, treated adult galactosemia patients continue to exhibit ongoing N-glycan processing defects. We have now applied informative galactose incorporation ratios as a method of studying the presence of N-glycan processing defects in children with galactosemia. We identified N-glycan processing defects present in galactosemia children from an early age. For G0/G1, G0/G2, and (G0/G1)/G2 ratios, the difference noted between galactosemia patients and controls was found to be statistically significant (p = 0.002, 0.01, and 0.006, respectively).
authors.affiliation: University College Dublin (UCD) , Clinical Research Centre, Mater Misericordiae University Hospital, Eccles Street, Dublin, Ireland.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Coss
authors.forename: Colin P
authors.initials: CP
authors.lastname: Hawkes
authors.forename: Barbara
authors.initials: B
authors.lastname: Adamczyk
authors.forename: Henning
authors.initials: H
authors.lastname: Stöckmann
authors.forename: Ellen
authors.initials: E
authors.lastname: Crushell
authors.forename: Radka
authors.initials: R
authors.lastname: Saldova
authors.forename: Ina
authors.initials: I
authors.lastname: Knerr
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.forename: Ardeshir A
authors.initials: AA
authors.lastname: Monavari
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Treacy
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D005693:Galactosemias / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D011134:Polysaccharides