Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

Introduction: Childhood epilepsy is one of the most common neurological problems. The transferrin isoelectric focusing (TIEF) test is a screening test for congenital disorders of glycosylation (CDG). We identified abnormal TIEF test in children with epilepsy in our epilepsy genetics clinic. To determine if an abnormal TIEF test is associated with anti-epileptic medications or abnormal liver functions, we performed a retrospective cohort study. Methods: This study was performed between January 2012 and March 2020. Electronic patient charts were reviewed. Standard non-parametric statistical tests were applied using R statistical software. Fischer’s exact test was used for comparisons. Results: There were 206 patients. The TIEF test was abnormal in 11% (23 out of 206) of the patients. Nine patients were diagnosed with CDG: PMM2-CDG (n = 5), ALG3-CDG (n = 1), ALG11-CDG (n = 2), SLC35A2-CDG (n = 1). We report 51 different genetic diseases in 84 patients. Two groups, (1) abnormal TIEF test; (2) normal TIEF test, showed statistically significant differences for abnormal liver functions and for valproic acid treatment. Conclusion: The TIEF test guided CDG diagnosis in 2.9% of the patients. Due to the high prevalence of CDG (4.4%) in childhood epilepsy, the TIEF test might be included into the diagnostic investigations to allow earlier and cost-effective diagnosis.

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Our Experience with Diagnostics of Congenital Disorders of Glycosylation

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2018.103 ◽

2004 ◽

Vol 47 (4) ◽

pp. 267-272 ◽

Cited By ~ 2

Author(s):

Ziad Albahri ◽

Eliška Marklová ◽

Hubert Vaníček ◽

Lenka Minxová ◽

Petr Dědek ◽

...

Keyword(s):

Metabolic Disease ◽

Isoelectric Focusing ◽

Congenital Disorders ◽

Serum Transferrin ◽

Congenital Disorders Of Glycosylation ◽

Healthy Controls ◽

Protein Variants

The aim of this study is to report our 3years experience with the screening of congenital disorders of glycosylation. A common isoelectric focusing method with immunofixation was used for analysis of serum transferrin and α1-antitrypsin, apart from several other procedures. A group of about 1000 individuals, both healthy controls and patients, mostly with signs of a metabolic disease were examined. Here we present an overview of 1) hypoglycosylation findings, 2) distribution of protein variants, 3) misguiding rare Tf variants found in our set, and 4) association of some phenotypes with various diseases.

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A Novel Homozygous ALG12 Mutation in a Patient with CDG Type Ig: New Report of a Case with a Mild Phenotype

Molecular Syndromology ◽

10.1159/000516606 ◽

2021 ◽

pp. 1-6

Author(s):

Antonio Gennaro Nicotera ◽

Giulia Spoto ◽

Francesco Calì ◽

Giusi Romeo ◽

Antonino Musumeci ◽

...

Keyword(s):

Autosomal Recessive ◽

Autosomal Dominant ◽

Genetic Diseases ◽

Failure To Thrive ◽

Congenital Disorders ◽

Homozygous Mutation ◽

Congenital Disorders Of Glycosylation ◽

Mild Phenotype ◽

Dysmorphic Features ◽

Rare Genetic Diseases

Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases caused by the deficiency of enzymes involved in the biosynthesis or remodeling of the glycan moieties of glycoconjugates. Most of CDG are autosomal recessive; however, few of them show autosomal dominant or X-linked inheritance. ALG12-CDG is an autosomal recessive inherited defect caused by a deficiency in the α-mannosyltransferase, dolichyl-P-mannose: Man7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (mannosyltransferase 8), which determines Man7GlcNAc2-PP-dolichol accumulation in tissues including fibroblasts. The clinical features of ALG12-CDG include dysmorphic features, developmental delay, hypotonia, progressive microcephaly, hypogammaglobulinemia, coagulopathies, and failure to thrive. Herein, we describe the case of a Sicilian patient with a milder phenotype bearing an <i>ALG12</i> homozygous mutation. To date, including this patient, only 16 cases have been described with this form of CDG. Furthermore, our study contributes to understanding the milder ALG12-CDG cases and to further expanding the genotype-phenotype spectrum.

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Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten‐year experience in a Brazilian center

Jornal de Pediatria (Versão em Português) ◽

10.1016/j.jpedp.2019.11.001 ◽

2020 ◽

Vol 96 (6) ◽

pp. 710-716

Author(s):

Ana Paula Pereira Scholz de Magalhães ◽

Maira Graeff Burin ◽

Carolina Fischinger Moura de Souza ◽

Fernanda Hendges de Bitencourt ◽

Fernanda Medeiros Sebastião ◽

...

Keyword(s):

Isoelectric Focusing ◽

Congenital Disorders ◽

Congenital Disorders Of Glycosylation

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Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center

Jornal de Pediatria ◽

10.1016/j.jped.2019.05.008 ◽

2020 ◽

Vol 96 (6) ◽

pp. 710-716

Author(s):

Ana Paula Pereira Scholz de Magalhães ◽

Maira Graeff Burin ◽

Carolina Fischinger Moura de Souza ◽

Fernanda Hendges de Bitencourt ◽

Fernanda Medeiros Sebastião ◽

...

Keyword(s):

Isoelectric Focusing ◽

Congenital Disorders ◽

Congenital Disorders Of Glycosylation

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Platelets and Defective N-Glycosylation

International Journal of Molecular Sciences ◽

10.3390/ijms21165630 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5630 ◽

Cited By ~ 1

Author(s):

Elmina Mammadova-Bach ◽

Jaak Jaeken ◽

Thomas Gudermann ◽

Attila Braun

Keyword(s):

Endoplasmic Reticulum ◽

Thermodynamic Stability ◽

Metabolic Pathways ◽

Genetic Diseases ◽

Congenital Disorders ◽

Congenital Disorders Of Glycosylation ◽

Abnormal Protein ◽

Rare Genetic Diseases ◽

Covalently Linked ◽

Asparagine Residue

N-glycans are covalently linked to an asparagine residue in a simple acceptor sequence of proteins, called a sequon. This modification is important for protein folding, enhancing thermodynamic stability, and decreasing abnormal protein aggregation within the endoplasmic reticulum (ER), for the lifetime and for the subcellular localization of proteins besides other functions. Hypoglycosylation is the hallmark of a group of rare genetic diseases called congenital disorders of glycosylation (CDG). These diseases are due to defects in glycan synthesis, processing, and attachment to proteins and lipids, thereby modifying signaling functions and metabolic pathways. Defects in N-glycosylation and O-glycosylation constitute the largest CDG groups. Clotting and anticlotting factor defects as well as a tendency to thrombosis or bleeding have been described in CDG patients. However, N-glycosylation of platelet proteins has been poorly investigated in CDG. In this review, we highlight normal and deficient N-glycosylation of platelet-derived molecules and discuss the involvement of platelets in the congenital disorders of N-glycosylation.

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Screening for congenital disorders of glycosylation (CDG): Transferrin HPLC versus isoelectric focusing (IEF)

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2008.12.013 ◽

2009 ◽

Vol 42 (4-5) ◽

pp. 408-415 ◽

Cited By ~ 17

Author(s):

Ester Quintana ◽

Aleix Navarro-Sastre ◽

José María Hernández-Pérez ◽

Judit García-Villoria ◽

Raquel Montero ◽

...

Keyword(s):

Isoelectric Focusing ◽

Congenital Disorders ◽

Congenital Disorders Of Glycosylation

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Transferrin isoform analysis from dried blood spots and serum samples by gel isoelectric focusing for screening congenital disorders of glycosylation

Acta Biochimica Polonica ◽

10.18388/abp.2020_5576 ◽

2021 ◽

Author(s):

Anna Bogdańska ◽

Dariusz Kozłowski ◽

Magdalena Pajdowska ◽

Patryk Lipiński ◽

Anna Tylki-Szymańska

Keyword(s):

Isoelectric Focusing ◽

Dried Blood Spots ◽

Dried Blood Spot ◽

Congenital Disorders ◽

Congenital Disorders Of Glycosylation ◽

Serum Samples ◽

Postmortem Diagnosis ◽

Glycoprotein Synthesis ◽

Gel Isoelectric Focusing ◽

Blood Spot

Congenital disorders of glycosylation (CDG) are a growing, heterogeneous group of genetic disorders caused by a defect in the glycoprotein synthesis. The first and still widely used method for routine CDG screening was isoelectric focusing (IEF) of serum transferrin. Dried blood spot (DBS) testing is commonly used in newborn screening procedures to detect inborn errors of metabolism. The aim of this study was to demonstrate the reliability of the IEF method in DBS testing. Dried blood spot testing can help in the postmortem diagnosis of CDG disorders when other material is unavailable. The patterns and concentrations of transferrin isoforms in serum and DBS are comparable, and slight differences do not affect interpretation of results.

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