Received on May 27, 2006
Accepted on November 14, 2006

Molecular Diagnostics and Genetics

Transferrin and Apolipoprotein C-III Isofocusing Are Complementary in the Diagnosis of N- and O-Glycan Biosynthesis Defects

¹ Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
² Department of Pediatric Metabolic Medicine and Institute for Child Health, Great Ormond Street Hospital, London, United Kingdom
³ Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
⁴ Institut National de la Santé et de la Recherche Médicale (INSERM U602), Groupement de Recherche, Paul Brousse Hospital, University of Paris Villejuif, France
⁵ Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

^* To whom correspondence should be addressed. E-mail: r.wevers{at}cukz.umcn.nl.

Background: Apolipoprotein C-III (apoC-III) isoelectric focusing (IEF) can be used to detect abnormalities in the biosynthesis of core 1 mucin-type O-glycans.

Methods: We studied plasma samples from 55 patients with various primary defects in N- and/or O-glycosylation, 21 patients with secondary N-glycosylation defects, and 6 patients with possible glycosylation abnormalities. Furthermore, we analyzed 500 plasma samples that were sent to our laboratory for selective screening for inborn errors of metabolism.

Results: Plasma samples from patients with congenital disorders of glycosylation (CDG) types -IIe and -IIf showed a hypoglycosylated apoC-III isoform profile, as did plasma samples from 75% of the patients with an unspecified CDG type II. Hyposialylated O-glycan profiles were also seen in plasma from 2 patients with hemolytic-uremic syndrome. In the 500 plasma samples from the selective screening, 3 patients were identified with a possible isolated defect in the biosynthesis of core 1 mucin-type O-glycans.

Conclusions: To our knowledge this is the first study in which use of a plasma marker protein has identified patients in whom only O-glycan biosynthesis might be affected. The primary defect(s) remain as yet unknown. Plasma apoC-III IEF is complementary to transferrin isofocusing. In conjunction both tests identify biosynthesis defects in N-glycan and mucin-type core 1 O-glycan biosynthesis. The apoC-III IEF assay is likely to help metabolic laboratories to identify and unravel further subtypes of inborn errors of glycan biosynthesis.