TY - JOUR
T1 - Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects
AU - Wopereis, Suzan
AU - Grünewald, Stephanie
AU - Huijben, Karin M.L.C.
AU - Morava, Éva
AU - Mollicone, Rosella
AU - Van Engelen, Baziel G.M.
AU - Lefeber, Dirk J.
AU - Wevers, Ron A.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
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U2 - 10.1373/clinchem.2006.073940
DO - 10.1373/clinchem.2006.073940
M3 - Article
C2 - 17170056
AN - SCOPUS:33847354287
SN - 0009-9147
VL - 53
SP - 180
EP - 187
JO - Clinical chemistry
JF - Clinical chemistry
IS - 2
ER -