Glycobiology Advance Access published online on July 21, 2005
Glycobiology, doi:10.1093/glycob/cwj017
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1 Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, The Netherlands
* To whom correspondence should be addressed. Defects in the biosynthesis of N- and core 1 O-glycans may be found by isoelectric focusing (IEF) of plasma transferrin and apolipoprotein C-III (apoC-III). We hypothesized that IEF of transferrin and apoC-III in combination with SDS-PAGE of apoC-III may provide a classification for CDG patients. We analyzed plasma from 22 patients with eight different and well-characterized CDG subtypes and 19 cases with unsolved CDG. Transferrin IEF has been used to distinguish between N-glycan assembly (type 1 profile) and processing (type 2 profile) defects. We differentiated two different CDG type 2 transferrin IEF profiles: The ‘asialo profile’ characterized by elevated levels of asialo- and monosialotransferrin and the ‘disialo profile’ characterized by increased levels of disialo- and trisialotransferrin. ApoC-III IEF gave two abnormal profiles (‘apoC-III0’ and ‘apoC-III1’ profiles). The results for the eight established CDG forms exactly matched the theoretical expectations, providing a validation for the study approach. The combination of the three electrophoretic techniques was not additionally informative for the CDG-Ix patients as they had normal apoC-III IEF patterns. However, the CDG-IIx patients could be further subdivided into six biochemical subgroups. The robustness of the methodology was supported by the fact that three patients with similar clinical features ended in the same subgroup and that another patient, classified in the ‘CDG-IIe subgroup’, turned out to have a similar defect. Dividing the CDG-IIx patients in six subgroups narrows down drastically the options for the primary defect in each of the subgroups and will be helpful to define new CDG type II defects.
Received April 25, 2005
Revised June 20, 2005
Accepted July 13, 2005
Article
Patients with unsolved congenital disorders of glycosylation type II can be subdivided in six distinct biochemical groups
2 Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, The Netherlands
3 Consultant Pediatric Metabolic Medicine, Great Ormond Street Hospital, London WC1N 3JH, United Kingdom
4 Laboratory of Diagnostics Department, The Children’s Memorial Health institute, Warsaw 04 730, Poland
Ron A Wevers, E-mail: r.wevers{at}cukz.umcn.nl
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