scholarly journals Congenital Disorders of Glycosylation: What Clinicians Need to Know?

2021 ◽  
Vol 9 ◽  
Author(s):  
Patryk Lipiński ◽  
Anna Tylki-Szymańska
Keyword(s):  
High Performance ◽  
Diagnostic Algorithm ◽  
Diagnostic Methods ◽  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation ◽  
Acid Deficiency ◽  
Zone Electrophoresis ◽  
Capillary Zone ◽  
Generation Sequencing

Congenital disorders of glycosylation (CDG) are a group of clinically heterogeneous disorders characterized by defects in the synthesis of glycans and their attachment to proteins and lipids. This manuscript aims to provide a classification of the clinical presentation, diagnostic methods, and treatment of CDG based on the literature review and our own experience (referral center in Poland). A diagnostic algorithm for CDG was also proposed. Isoelectric focusing (IEF) of serum transferrin (Tf) is still the method of choice for diagnosing N-glycosylation disorders associated with sialic acid deficiency. Nowadays, high-performance liquid chromatography, capillary zone electrophoresis, and mass spectrometry techniques are used, although they are not routinely available. Since next-generation sequencing became more widely available, an improvement in diagnostics has been observed, with more patients and novel CDG subtypes being reported. Early and accurate diagnosis of CDG is crucial for timely implementation of appropriate therapies and improving clinical outcomes. However, causative treatment is available only for few CDG types.

A NEW CAPILLARY ZONE ELECTROPHORESIS METHOD FOR THE SCREENING OF CONGENITAL DISORDERS OF GLYCOSYLATION (CDG)

2009 ◽  
Vol 32 (6S) ◽  
pp. 7
Author(s):  
F Parente ◽  
N Ah Mew ◽  
J Jaeken ◽  
B M Gilfix
Keyword(s):  
Capillary Zone Electrophoresis ◽  
Metabolic Diseases ◽  
Clinical Syndrome ◽  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation ◽  
Serum Samples ◽  
Significant Difference ◽  
Zone Electrophoresis ◽  
Capillary Zone ◽  
Guthrie Cards

Background: The Congenital Disorders of Glycosylation (CDG) are an expanding group of metabolic diseases with a broad clinical presentation. We sought to validate a new Capillary Zone Electrophoresis (CZE) method (Sebia CAPILLARYS™ CDT) to screen for CDG. Methods: We analyzed 119 serum samples from children of varying ages and of both sexes to establish a reference range of transferrin glycoforms including CDT (Carbohydrate Deficient Transferrin). We then studied serums from 8 known CDG patients and compared the CZE results to the isoelectric focusing (IEF) profiles. We also analyzed serums after extraction from spotted Guthrie cards. Results: The mean (SD) percentage of transferrin glycoforms is 18.5 (4.4), 78.5 (4.2), 2.5 (1.3) and 0.6 (0.3) for penta-, tetra-, trisialotransferrin and CDT, respectively. There is no statistically significant difference between the different age groups analyzed (0-5, 6-11, 12-15, 16-18, and > 18 years) or between sexes. We observed a good correlation between the CZE and IEF profiles with both fresh serum and serum extracted from Guthrie cards. Conclusions: The Sebia CAPILLARYS™ CDT system is a simple and reliable method to screen for CDG in pediatric and adult patients with an unexplained clinical syndrome, particularly when the nervous system is involved.

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

2004 ◽  
Vol 50 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Hubert A Carchon ◽  
Roland Chevigné ◽  
Jean-Bernard Falmagne ◽  
Jaak Jaeken
Keyword(s):  
Capillary Zone Electrophoresis ◽  
Reference Group ◽  
Congenital Disorders ◽  
Serum Transferrin ◽  
Congenital Disorders Of Glycosylation ◽  
Zone Electrophoresis ◽  
Carbohydrate Deficient Transferrin ◽  
Group A ◽  
Capillary Zone ◽  
Relative Migration

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 CEofixTM-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.

Why is the novel Hb Miguel Servet visualised by CE-HPLC newborn and not by the CE-HPLC β-thalassaemia programme?

2020 ◽  
pp. jclinpath-2020-206812
Author(s):  
Valle Recasens ◽  
Ángeles Montañés ◽  
Carmen Rodríguez-Vigil ◽  
Yolanda González ◽  
Guillermo Hernández de Abajo ◽  
...  
Keyword(s):  
High Performance ◽  
Globin Genes ◽  
The Novel ◽  
Adequate Treatment ◽  
Zone Electrophoresis ◽  
Capillary Zone ◽  
Hb Variant ◽  
Unexpected Findings ◽  
Β Chain ◽  
Genetic Analyzer

Screening of haemoglobinopathies is indicated for the detection of sickle cell anaemia; thus, neonates can benefit from early and adequate treatment that prevents neurological damage, reduces morbidity and mortality associated with the disease. These types of programmes sometimes lead to unexpected findings. We present a new haemoglobin (Hb) variant (Hb Miguel Servet) detected by newborn screening. During neonatal screening of haemoglobinopathies by cation-exchange high-performance liquid chromatography (CE-HPLC) newborn, an Hb variant was detected. An analysis at 8 months of age using capillary zone electrophoresis (CZE) confirmed the presence of this new Hb. The molecular characterisation was performed by automatic sequencing of the α and β globin genes in an ABI PRISM 3100 Genetic Analyzer. Hb analysis by CE-HPLC β-thalassaemia short programmedid not indicate the presence of abnormal Hbs. By CZE showed a peak in the zone 12 zone comprising 3.3% of the total Hb. A new analysis by CE-HPLC on a Tosoh G8-2 (Horiba) shown a peak, in the region of HbA1b, did not interfere with the quantification of HbA1c. Sequencing of the β gene revealed the substitution of a guanine for a thymine (GGT >TGT) in codon 69 of the second exon, resulting in substitution of cysteine for the amino acid glutamine (HBB:c.208G>T). Hb Miguel Servet is a β-chain globin variant detected by CE-HPLC newborn (BioRad), by CZE and by CE-HPLC-CE Tosoh G8-2 (Horiba), but no by CE-HPLC-CE β-thalassaemia short programme (BioRad). In fact, for all the techniques that are visualised, what would be detected would be the glutathione variant of Hb (Miguel Servet).

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