Increased fucosylation and branching of serum transferrin N-glycans in long-term untreated Galactosemic patients (Articolo in rivista)

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Label
  • Increased fucosylation and branching of serum transferrin N-glycans in long-term untreated Galactosemic patients (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Alternative label
  • L.Sturiale, R.Barone, G.Sorge, M.Zaffanello, A.Fiumara, G.Impallomeni, D.Garozzo (2004)
    Increased fucosylation and branching of serum transferrin N-glycans in long-term untreated Galactosemic patients
    in Glycobiology (Oxf.)
    (literal)
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  • L.Sturiale, R.Barone, G.Sorge, M.Zaffanello, A.Fiumara, G.Impallomeni, D.Garozzo (literal)
Pagina inizio
  • 1154 (literal)
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  • 14 (literal)
Rivista
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  • No. Citazione=0; Autocitazione=0; Motore utilizzato per le citazioni=Isiwebofknowledge.com (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • CNR, Università di Catania, Università di Verona, Mayo Clinic and Foundation, Centre for Metabolic Disease. (literal)
Titolo
  • Increased fucosylation and branching of serum transferrin N-glycans in long-term untreated Galactosemic patients (literal)
Abstract
  • Galactosemia is an autosomal recessive disorder caused, in the most common form, by mutation in the galactose-1-phosphate uridyltransferase (GALT) gene (ch. 9p13). The resulting enzyme deficiency leads to anomalous accumulation of galactose and gatactose-1-phosphate in blood and tissues and produces severe symptoms as mental retardation, cirrhosis of the liver and cataracts, prevented by a galactose-free diet. In untreated galactosemic patients, isoform patterns of serum transferrin, lysosomal enzymes b-hexosaminidase and a-fucosidase and follicle stimulating hormone are abnormal, due to the increase of relatively neutral isoforms corresponding to less sialylated carbohydrate structures [1-2]. These evidences are similar to those observed in the Congenital Disorders of Glycosylation (CDG) which are inherited disorders characterized by a defective synthesis of the carbohydrate moiety of multiple serum glycoproteins. In order to investigate the glycosylation abnormalities in galactosemic patients, we used MALDI mass spectrometry to individuate the glycosylation degree of intact glycoproteins and to achieve the fully characterization of the N-linked oligosaccharide structures. Particularly, we focused on the glycosylation pattern of rivanol purified serum transferrin (the classical biochemical marker of CDGs) in two galactosemia patients before treatment and during follow-up on galactose-free diet. The results were compared with those obtained in subjects with CDG-Ia (PMM deficiency) and healthy controls. The galactosemic patients were both overexposed to dietary galactose (11 and 5 weeks respectively) because of an initial false negative newborn screening following red blood cell transfusion. In long-term untreated galactosemia we found a severe underoccupancy of both transferrin N-glycosylation sites according to the isoelectric focusing pattern and the profile of MALDI-TOF mass spectra of the intact glycoprotein. Release of N-glycans after PNGase F digestion of the same samples, followed by MALDI-TOF analysis both in negative and in positive polarity, revealed a great heterogeneity of glycoforms ranging from truncated biantennary species deprived of sialic acid and/or galactose, to triantennary and tetraantennary species at higher molecular weight. Moreover, we found a significant increase of the fucosylation degree of all the glycoforms, already reported for CDG-I [3], but never observed before in galactosemia. Such abnormal findings were not observed upon dietary treatment. These evidences suggest that in long-term untreated galactosemia, defects in both the assembly as well as in the processing pathways may occur. These findings open the way to a better comprehension of the biochemical mechanisms regarding the defective glycosylation pathway in galactosemia. (literal)
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