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

Suzan Wopereis, Stephanie Grünewald, Eva Morava-Kozicz, Johannes M. Penzien, Paz Briones, M. Teresa García-Silva, Pierre N.M. Demacker, Karin M.L.C. Huijben, Ron A. Wevers

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1839-1845
Number of pages7
JournalClinical Chemistry
Volume49
Issue number11
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

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Apolipoprotein C-III
Biosynthesis
Polysaccharides
Defects
Glycosylation
Mucin-1
Plasmas
Hemolytic-Uremic Syndrome
Isoelectric Focusing
Congenital Disorders of Glycosylation
Inborn Errors Metabolism
Neuraminidase
N-Acetylneuraminic Acid
Transferrin
Streptococcus pneumoniae
Galactose
Metabolism
Assays
Screening
Protein Isoforms

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Wopereis, S., Grünewald, S., Morava-Kozicz, E., Penzien, J. M., Briones, P., García-Silva, M. T., ... Wevers, R. A. (2003). Apolipoprotein C-III Isofocusing in the Diagnosis of Genetic Defects in O-Glycan Biosynthesis. Clinical Chemistry, 49(11), 1839-1845. https://doi.org/10.1373/clinchem.2003.022541

Apolipoprotein C-III Isofocusing in the Diagnosis of Genetic Defects in O-Glycan Biosynthesis. / Wopereis, Suzan; Grünewald, Stephanie; Morava-Kozicz, Eva; Penzien, Johannes M.; Briones, Paz; García-Silva, M. Teresa; Demacker, Pierre N.M.; Huijben, Karin M.L.C.; Wevers, Ron A.

In: Clinical Chemistry, Vol. 49, No. 11, 01.11.2003, p. 1839-1845.

Research output: Contribution to journalArticle

Wopereis, S, Grünewald, S, Morava-Kozicz, E, Penzien, JM, Briones, P, García-Silva, MT, Demacker, PNM, Huijben, KMLC & Wevers, RA 2003, 'Apolipoprotein C-III Isofocusing in the Diagnosis of Genetic Defects in O-Glycan Biosynthesis', Clinical Chemistry, vol. 49, no. 11, pp. 1839-1845. https://doi.org/10.1373/clinchem.2003.022541
Wopereis, Suzan ; Grünewald, Stephanie ; Morava-Kozicz, Eva ; Penzien, Johannes M. ; Briones, Paz ; García-Silva, M. Teresa ; Demacker, Pierre N.M. ; Huijben, Karin M.L.C. ; Wevers, Ron A. / Apolipoprotein C-III Isofocusing in the Diagnosis of Genetic Defects in O-Glycan Biosynthesis. In: Clinical Chemistry. 2003 ; Vol. 49, No. 11. pp. 1839-1845.
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abstract = "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.",
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AU - Wopereis, Suzan

AU - Grünewald, Stephanie

AU - Morava-Kozicz, Eva

AU - Penzien, Johannes M.

AU - Briones, Paz

AU - García-Silva, M. Teresa

AU - Demacker, Pierre N.M.

AU - Huijben, Karin M.L.C.

AU - Wevers, Ron A.

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N2 - 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.

AB - 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.

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