HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (32) Citing Articles via Google Scholar Google Scholar Articles by Wopereis, S. Articles by Wevers, R. A. Search for Related Content PubMed PubMed Citation Articles by Wopereis, S. Articles by Wevers, R. A. Related Collections Molecular Diagnostics and Genetics

Apolipoprotein C-III Isofocusing in the Diagnosis of Genetic Defects in O-Glycan Biosynthesis

University Medical Center Nijmegen,
¹ Laboratory of Pediatrics and Neurology,
² Department of Pediatrics, and
³ General Internal Medicine, NL-6525 GC Nijmegen, The Netherlands.
⁴ University Hospital of Essen, Center for Peadiatrics, D-45122 Essen, Germany.

⁵ Children’s Hospital, Department of Neuropaediatrics, D-86156 Augsburg, Germany.

⁶ Corporació Sanitària Clínic, Institut de Bioquímica Clínica, E-08036 Barcelona, Spain.

⁷ Hospital Universitario 12 de Octubre, Departamento de Pediatria, E-28041 Madrid, Spain.

^aAddress correspondence to this author at: University Medical Center Nijmegen, Laboratory of Pediatrics and Neurology (319), Institute of Neurology, Reinier Postlaan 4, 6525 GC Nijmegen, The Netherlands. Fax 31-24-3540297; e-mail r.wevers{at}cukz.umcn.nl.

Background: Defects in the biosynthesis of N-glycans may be found by isoelectric focusing (IEF) of plasma transferrin. No test is available to demonstrate O-glycan biosynthesis defects.

Methods: We used isoforms of apolipoprotein C-III (apoC-III) as a marker for the biosynthesis of core 1 mucin type O-glycans. Plasma samples from patients with primary defects and secondary alterations in N-glycan biosynthesis were studied by apoC-III isofocusing.

Results: Age-related reference values for apoC-III were determined. Plasma samples from patients with the primary congenital disorders of glycosylation (CDG) types Ia–Ic, Ie, If, IIa, and IId all showed a normal apoC-III isofocusing profile. Plasma from two patients with CDG type IIx were tested: one showed a normal apoC-III distribution, whereas the other showed a hypoglycosylation profile. In plasma from patients with hemolytic uremic syndrome (HUS), a hypoglycosylation profile was obtained.

Conclusions: IEF of apoC-III is a rapid and simple technique that may be used as a screening assay for abnormalities in core 1 mucin type O-glycans. Evidence that a patient in this study has a primary genetic defect affecting both N- and O-glycosylation provides the first example of an inborn error of metabolism affecting the biosynthesis of core 1 mucin type O-glycans. Our data narrow the options for the position of the primary defect in this patient down to a step in the biosynthesis, activation, or transfer of galactose or N-acetylneuraminic acid to both N- and O-glycans. Circulating neuraminidase excreted by Streptococcus pneumoniae caused the high percentage of asialo apoC-III in two HUS patients.

The following articles in journals at HighWire Press have cited this article:

				L. Van Maldergem, M. Yuksel-Apak, H. Kayserili, E. Seemanova, S. Giurgea, L. Basel-Vanagaite, E. Leao-Teles, J. Vigneron, M. Foulon, M. Greally, et al. Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debre type Neurology, November 11, 2008; 71(20): 1602 - 1608. [Abstract] [Full Text] [PDF]

				F. Foulquier, D. Ungar, E. Reynders, R. Zeevaert, P. Mills, M. T. Garcia-Silva, P. Briones, B. Winchester, W. Morelle, M. Krieger, et al. A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation Hum. Mol. Genet., April 1, 2007; 16(7): 717 - 730. [Abstract] [Full Text] [PDF]

				G. M. Olson, D. S. Fox, P. Wang, J. A. Alspaugh, and K. L. Buchanan Role of Protein O-Mannosyltransferase Pmt4 in the Morphogenesis and Virulence of Cryptococcus neoformans Eukaryot. Cell, February 1, 2007; 6(2): 222 - 234. [Abstract] [Full Text] [PDF]

				S. Wopereis, S. Grunewald, K. M.L.C. Huijben, E. Morava, R. Mollicone, B. G.M. van Engelen, D. J. Lefeber, and R. A. Wevers Transferrin and Apolipoprotein C-III Isofocusing Are Complementary in the Diagnosis of N- and O-Glycan Biosynthesis Defects Clin. Chem., February 1, 2007; 53(2): 180 - 187. [Abstract] [Full Text] [PDF]

				S. Wopereis, D. J. Lefeber, E. Morava, and R. A. Wevers Mechanisms in Protein O-Glycan Biosynthesis and Clinical and Molecular Aspects of Protein O-Glycan Biosynthesis Defects: A Review Clin. Chem., April 1, 2006; 52(4): 574 - 600. [Abstract] [Full Text] [PDF]

				F. Foulquier, E. Vasile, E. Schollen, N. Callewaert, T. Raemaekers, D. Quelhas, J. Jaeken, P. Mills, B. Winchester, M. Krieger, et al. Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II. PNAS, March 7, 2006; 103(10): 3764 - 3769. [Abstract] [Full Text] [PDF]

				S. Wopereis, E. Morava, S. Grunewald, M. Adamowicz, K. M. L. C. Huijben, D. J. Lefeber, and R. A. Wevers Patients with unsolved congenital disorders of glycosylation type II can be subdivided in six distinct biochemical groups Glycobiology, December 1, 2005; 15(12): 1312 - 1319. [Abstract] [Full Text] [PDF]