IgG N-glycans as potential biomarkers for determining galactose tolerance in Classical Galactosaemia

N-glycan processing and assembly defects have been demonstrated in untreated and partially treated patients with Classical Galactosaemia. These defects may contribute to the ongoing pathophysiology of this disease. The aim of this study was to develop an informative method of studying differential g...

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Bibliographic Details
Published in:	Molecular genetics and metabolism Vol. 105; no. 2; pp. 212 - 220
Main Authors:	Coss, K.P., Byrne, J.C., Coman, D.J., Adamczyk, B., Abrahams, J.L., Saldova, R., Brown, A.Y., Walsh, O., Hendroff, U., Carolan, C., Rudd, P.M., Treacy, E.P.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-02-2012
Subjects:	Adult Biochemical markers Biomarkers Biomarkers, Pharmacological Diet Diet liberalization Diets Drug Tolerance Erythrocytes Female Galactosaemia Galactose Galactose - administration & dosage Galactose - metabolism Galactosemia Galactosemias - economics Galactosemias - metabolism Galactosemias - therapy Galactosylation Glycosylation High-performance liquid chromatography Humans IgG N-glycans Immunoglobulin G Immunoglobulin G - immunology Immunoglobulin G - metabolism Male N-glycans NP-HPLC Nutrient deficiency Polysaccharides - immunology Polysaccharides - metabolism GALT IgG N-glycans G0 G1 G2 Diet liberalization Galactosylation NP-HPLC Galactosaemia ABS RBC Gal Biomarkers BKF UDP-Gal Gal-1-P
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Summary:	N-glycan processing and assembly defects have been demonstrated in untreated and partially treated patients with Classical Galactosaemia. These defects may contribute to the ongoing pathophysiology of this disease. The aim of this study was to develop an informative method of studying differential galactose tolerance levels and diet control in individuals with Galactosaemia, compared to the standard biochemical markers. Ten Galactosaemia adults with normal intellectual outcomes were analyzed in the study. Five subjects followed galactose liberalization, increments of 300 mg to 4000 mg/day over 16 weeks, and were compared to five adult Galactosaemia controls on a galactose restricted diet. All study subjects underwent clinical and biochemical monitoring of red blood cell galactose-1-phosphate (RBC Gal-1-P) and urinary galactitol levels. Serum N-glycans were isolated and analyzed by normal phase high-performance liquid chromatography (NP-HPLC) with galactosylation of IgG used as a specific biomarker of galactose tolerance. IgG N-glycan profiles showed consistent individual alterations in response to diet liberalization. The individual profiles were improved for all, but one study subject, at a galactose intake of 1000 mg/day, with decreases in agalactosylated (G0) and increases in digalactosylated (G2) N-glycans. We conclude that IgG N-glycan profiling is an improved method of monitoring variable galactosylation and determining individual galactose tolerance in Galactosaemia compared to the standard methods. ► Galactosaemia is a potentially modifiable systemic glycosylation defect. ► N-glycan analysis is a new method of identifying variable N-glycosylation in Galactosaemia. ► N-glycan defects persist in treated Classical Galactosaemia subjects.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1096-7192 1096-7206
DOI:	10.1016/j.ymgme.2011.10.018