Comparison of transferrin isoform analysis by capillary electrophoresis and HPLC for screening congenital disorders of glycosylation

Dave, Mihika B.; Dherai, Alpa J.; Udani, Vrajesh; Hegde, Anaita Udwadia; Desai, Nayan; Ashavaid, Tester F.

doi:10.1002/jcla.22167

Cited by 12 publications

(17 citation statements)

References 28 publications

(37 reference statements)

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“…Despite the relative rarity of many of these disorders, the reason for inclusion is the treatability of some of these conditions. It is noteworthy that the transferrin isoform assays have often been established for monitoring relapse of alcoholism and thus may not be designed, analysed, interpreted or reported with consideration for congenital disorders of N-glycosylation [31]. Apolipoprotein-CIII isoform analysis is used to screen for congenital disorders of O-glycosylation [32][33][34].…”

Section: First-tier Testsmentioning

confidence: 99%

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

Mordaunt

Cox

Fuller

2020

IJMS

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Early diagnosis of inborn errors of metabolism (IEM)—a large group of congenital disorders—is critical, given that many respond well to targeted therapy. Newborn screening programs successfully capture a proportion of patients enabling early recognition and prompt initiation of therapy. For others, the heterogeneity in clinical presentation often confuses diagnosis with more common conditions. In the absence of family history and following clinical suspicion, the laboratory diagnosis typically begins with broad screening tests to circumscribe specialised metabolite and/or enzyme assays to identify the specific IEM. Confirmation of the biochemical diagnosis is usually achieved by identifying pathogenic genetic variants that will also enable cascade testing for family members. Unsurprisingly, this diagnostic trajectory is too often a protracted and lengthy process resulting in delays in diagnosis and, importantly, therapeutic intervention for these rare conditions is also postponed. Implementation of mass spectrometry technologies coupled with the expanding field of metabolomics is changing the landscape of diagnosing IEM as numerous metabolites, as well as enzymes, can now be measured collectively on a single mass spectrometry-based platform. As the biochemical consequences of impaired metabolism continue to be elucidated, the measurement of secondary metabolites common across groups of IEM will facilitate algorithms to further increase the efficiency of diagnosis.

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Section: First-tier Testsmentioning

confidence: 99%

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

Mordaunt

Cox

Fuller

2020

IJMS

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“…Following excessive alcohol ingestion for extended time periods, the amounts of less glycosylated forms of Tf (disialo-Tf > 2%, monosialo-Tf, and asialo-Tf) are increasing. Less glycosylated forms of Tf are also found in sera of CDG patients [23,24,[28][29][30][31][32][33][34], CSF [24], and can be produced in vitro by addition of neuraminidase to serum [16].…”

Section: Resultsmentioning

confidence: 99%

“…The latter system comprises polymeric polyions that form a dynamic double coating, an approach that leads to highly reproducible data [16], and was optimized for high-resolution analyses in our laboratory [17], which is advantageous for analysis of patient sera with unusual Tf patterns, including those with high amounts of trisialo-Tf and genetic variants [23][24][25][26][27]. CDG serum Tf patterns using the CEofix approach [11,23,28,29], the CAPILLARYS assay [30,31], and laboratory-made assays [32][33][34][35] have been reported. Furthermore, CZE was also used to determine CDG Tf patterns in extracts from Guthrie cards onto which the patient serum was applied [30,36].…”

Section: Introductionmentioning

confidence: 99%

High‐resolution capillary zone electrophoresis for transferrin glycoform analysis associated with congenital disorders of glycosylation

Tobler

Caslavska

Burda

et al. 2018

J of Separation Science

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High-resolution capillary zone electrophoresis is used to assess the transferrin profile in serum of patients with eight different congenital disorders of glycosylation that represent type I, type II, and mixed type I/II disorders. Capillary zone electrophoresis data are compared to patterns obtained by gel isoelectric focusing. The high-resolution capillary zone electrophoresis method is shown to represent an effective tool to assess the diversity of transferrin patterns. Hypoglycosylated disialo-, monosialo-, and asialo-transferrin in type I cases can be distinguished from the corresponding underdesialylated transferrin glycoforms present in type II disorders. The latter can be separated from and detected ahead of their corresponding hypoglycosylated forms of type I patients. Both types of glycoforms are detected in sera of mixed type I/II patients. The assay has the potential to be used as screening method for congenital disorders of glycosylation. It can be run with a few microliters of serum when microvials are used.

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“…CDG syndromes are diagnosed in sera of newborns, infants, and children using mainly gel IEF [14,16]. HPLC [5,14] and CZE [15,65,67,94,133,[147][148][149][150][151] assays were reported as screening methodologies for CDG by several laboratories. The popularity of these techniques is increasing.…”

Section: Other Applications and Special Aspects Of Tf Isoform Analysismentioning

confidence: 99%

“…2C were obtained with the HR-CEofix assay. Other laboratories employed the CEofix assay [15,147,150], the CAPPILARYS assay [149,151], and laboratory-made assays [67,94,148]. One group used CE-ESI-MS to identify glycoforms [94,148].…”

Section: Other Applications and Special Aspects Of Tf Isoform Analysismentioning

confidence: 99%

Monitoring of transferrin isoforms in biological samples by capillary electrophoresis

Caslavska

Thormann

2017

J of Separation Science

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Work dealing with the monitoring of transferrin isoforms in human serum and other body fluids by capillary electrophoresis is reviewed. It comprises capillary zone electrophoresis and capillary isoelectric focusing efforts that led to the exploration and use of assays for the determination of carbohydrate‐deficient transferrin as a marker for excessive alcohol intake, genetic variants of transferrin, congenital disorders of glycosylation and β‐2‐transferrin, which is a marker for cerebrospinal fluid leakage. This paper provides insight into the development, specifications, strengths, weaknesses, and routine use of the currently known capillary electrophoresis based assays suitable to detect transferrin isoforms in body fluids. The achievements reached so far indicate that capillary zone electrophoresis is an attractive technology to monitor the molecular forms of transferrin in biological specimens as the assays do not require an elaborate sample pretreatment and thus can be fully automated for high‐throughput analyses on multicapillary instruments. Assays based on capillary isoelectric focusing are less attractive. They require immunoextraction of transferrin from the biological matrix and mobilization after focusing if instrumentation with a whole‐column imaging detector is not available. Interactions of the carrier ampholytes with the iron of transferrin may prevent iron saturation and thus provide more complicated isoform patterns.

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Comparison of transferrin isoform analysis by capillary electrophoresis and HPLC for screening congenital disorders of glycosylation

Abstract: The CE method is rapid, reproducible and comparable with HPLC and can be used for screening Glycosylation defects.

Cited by 12 publications

References 28 publications

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

High‐resolution capillary zone electrophoresis for transferrin glycoform analysis associated with congenital disorders of glycosylation

Monitoring of transferrin isoforms in biological samples by capillary electrophoresis

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