Diagnosis of congenital disorders of glycosylation by capillary zone electrophoresis of serum transferrin.
BACKGROUND
Congenital disorders of glycosylation (CDG) are usually diagnosed by isoelectric focusing (IEF) of serum transferrin (Tf). The aim of this study was to evaluate capillary zone electrophoresis (CZE) as a diagnostic alternative to IEF.


METHODS
We performed 792 CZE analyses of Tf, using the CEofix(TM)-CDT (carbohydrate-deficient transferrin) assay. Peak identification was based on relative migration times (RMTs) to reduce migration variability.


RESULTS
Tf profiles comprised three main groups (A-C). Groups A and B were characterized by one or two dominant tetrasialo-Tf peaks, whereas group C showed a widely variable Tf isoform composition. Group A was composed of four subgroups: a major group with a typical Tf profile (considered as reference group), two minor groups with decreased or moderately increased trisialo-Tf isoform, and a group showing the presence of unknown compounds with RMTs similar to mono- and disialo-Tf. However, these compounds were absent on IEF. Group C contained all profiles from patients with confirmed as well as putative CDG. From the reference group, 99% confidence intervals were calculated for the RMTs of the Tf isoforms, and percentiles representing the Tf isoform distributions were defined.


CONCLUSIONS
All patients with abnormal IEF results and confirmed CDG were identified by CZE; thus, this method can be used as a diagnostic alternative to IEF in a manner suitable for automation. Because whole serum is analyzed, it should be kept in mind that CZE profiles can show substances other than Tf.
Carchon
Hubert A
HA
Department of Pediatrics, Center for Metabolic Disease, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium. hubert.carchon@med.kuleuven.ac.be
Chevigné
Roland
R
Falmagne
Jean-Bernard
JB
Jaeken
Jaak
J
D000293:Adolescent; D002239:Carbohydrate Metabolism, Inborn Errors / Q000175:diagnosis*; D019075:Electrophoresis, Capillary; D005260:Female; D006031:Glycosylation; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D020033:Protein Isoforms; D044967:Serum; D014168:Transferrin / Q000032:analysis*
D020033:Protein Isoforms; D014168:Transferrin