N-Glycan Abnormalities in Children with Galactosemia

Karen P. Coss, Colin P. Hawkes, Barbara Adamczyk, Henning Stoeckmann, Ellen Crushell, Radka Saldova, Ina Krierr, Maria E. Rubio-Gozalbo, Ardeshir A. Monavari, Pauline M. Rudd, Eileen P. Treacy*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 la) 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).
Original languageEnglish
Pages (from-to)385-394
JournalJournal of Proteome Research
Issue number2
Publication statusPublished - Feb 2014


  • galactosemia
  • children
  • IgG
  • glycan analysis
  • N-glycan processing abnormalities

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