Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects.
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.
Wopereis
Suzan
S
Department of Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Grünewald
Stephanie
S
Huijben
Karin M L C
KM
Morava
Eva
E
Mollicone
Rosella
R
van Engelen
Baziel G M
BG
Lefeber
Dirk J
DJ
Wevers
Ron A
RA
D000293:Adolescent; D053305:Apolipoprotein C-III / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006031:Glycosylation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007525:Isoelectric Focusing; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood* / Q000235:genetics; D011134:Polysaccharides / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000097:blood; D012189:Retrospective Studies; D014168:Transferrin / Q000378:metabolism*
D053305:Apolipoprotein C-III; D011134:Polysaccharides; D020033:Protein Isoforms; D014168:Transferrin