Diagnosis of Congenital Disorders of Glycosylation by Capillary Zone Electrophoresis of Serum Transferrin

Abstract

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.

Development and Multicenter Evaluation of the N Latex CDT Direct Immunonephelometric Assay for Serum Carbohydrate-Deficient Transferrin

“…Use of the N Latex CDT assay may therefore decrease the need for confirmatory CDT testing by HPLC or capillary electrophoresis (36 ). Additional studies are needed to confirm that other transferrin genetic variants and samples with divergent N-glycan structures, such as those occurring in the CDG subtypes, do not interfere with the N Latex CDT assay (22,37,38 ).…”

Reduced Sialylation Impacts Ventricular Repolarization by Modulating Specific K+ Channel Isoforms Distinctly

“…However, because sialic acids are typically the terminal glycan residue, any disease, including the different CDG, that disrupt gene products acting proximally to sialyltransferases, would also effectively reduce sialylation. Thus, the preliminary diagnostic test for all CDG is isoelectric focusing of transferrin, in which the results of the assay directly correspond to the number of sialic acids on the protein (58). Altered glycosylation was also reported in diseases and disease models of acquired etiology, such as Chagas disease, alcoholism, heart failure, and diabetes (53, 54, 59 -62).…”

DPAGT1 myasthenia and myopathy

“…These tests were performed at the Metabolic Center of the University of Leuven, Belgium, as described. 23 RESULTS Clinical features. Patient 1 is one of 8 siblings.…”