title: Hypoglycosylation with increased fucosylation and branching of serum transferrin N-glycans in untreated galactosemia.
abstract: Untreated classic galactosemia (galactose-1-phosphate uridyltransferase [GALT] deficiency) is known as a secondary congenital disorders of glycosylation (CDG) characterized by galactose deficiency of glycoproteins and glycolipids (processing defect or CDG-II). The mechanism of this undergalactosylation has not been established. Here we show that in untreated galactosemia, there is also a partial deficiency of whole glycans of serum transferrin associated with increased fucosylation and branching as seen in genetic glycosylation assembly defects (CDG-I). Thus galactosemia seems to be a secondary "dual" CDG causing a processing as well as an assembly N-glycosylation defect. We also demonstrated that in galactosemia patients, transferrin N-glycan biosynthesis is restored upon dietary treatment.
authors.affiliation: Istituto di Chimica e Tecnolgia dei Polimeri, CNA, Viale Regina Margherita 6, I-95123 Catania, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sturiale
authors.forename: Rita
authors.initials: R
authors.lastname: Barone
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.forename: Marta
authors.initials: M
authors.lastname: Perez
authors.forename: Marco
authors.initials: M
authors.lastname: Zaffanello
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorge
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pavone
authors.forename: Silvia
authors.initials: S
authors.lastname: Tortorelli
authors.forename: John F
authors.initials: JF
authors.lastname: O'Brien
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: Domenico
authors.initials: D
authors.lastname: Garozzo
mesh_terms: D001665:Binding Sites; D002853:Chromatography, Liquid; D005643:Fucose / Q000737:chemistry*; D005690:Galactose / Q000494:pharmacology; D005693:Galactosemias / Q000097:blood / Q000235:genetics*; D006017:Glycolipids / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007525:Isoelectric Focusing; D008297:Male; D011134:Polysaccharides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature; D014168:Transferrin / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D006017:Glycolipids; D006023:Glycoproteins; D007477:Ions; D011134:Polysaccharides; D014168:Transferrin; D005643:Fucose; D005690:Galactose