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The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant

Background: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic h...

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Autores principales: Paprocka, Justyna, Jezela-Stanek, Aleksandra, Boguszewicz, Łukasz, Sokół, Maria, Lipiński, Patryk, Jamroz, Ewa, Emich-Widera, Ewa, Tylki-Szymańska, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004727/
https://www.ncbi.nlm.nih.gov/pubmed/33807002
http://dx.doi.org/10.3390/children8030251
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author Paprocka, Justyna
Jezela-Stanek, Aleksandra
Boguszewicz, Łukasz
Sokół, Maria
Lipiński, Patryk
Jamroz, Ewa
Emich-Widera, Ewa
Tylki-Szymańska, Anna
author_facet Paprocka, Justyna
Jezela-Stanek, Aleksandra
Boguszewicz, Łukasz
Sokół, Maria
Lipiński, Patryk
Jamroz, Ewa
Emich-Widera, Ewa
Tylki-Szymańska, Anna
author_sort Paprocka, Justyna
collection PubMed
description Background: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity. This manuscript describes the first metabolomic analysis using NMR in three patients with epileptic encephalopathy due to the recurrent c.320A>G variant in ALG13, characterized to date only in about 60 individuals (mostly female). This is an important preliminary step in the understanding of the pathogenesis of the disease associated with this variant in the rare genetic condition. The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein. Despite this, protein electrophoresis, which is abnormal in most conditions due to abnormalities in N-glycosylation, has been normal or only mildly abnormal in the ALG13 patients. Methods: Nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate and univariate modelling were used to analyze the metabolic profile of the blood serum samples acquired from the studied patients. Results: Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine. Conclusions: Since presented data are the first to be collected so far, they need be verified in further studies. Our intention was to turn attention toward possible CDG-ALG13 laboratory markers that would have clinical significance.
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spelling pubmed-80047272021-03-29 The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant Paprocka, Justyna Jezela-Stanek, Aleksandra Boguszewicz, Łukasz Sokół, Maria Lipiński, Patryk Jamroz, Ewa Emich-Widera, Ewa Tylki-Szymańska, Anna Children (Basel) Article Background: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity. This manuscript describes the first metabolomic analysis using NMR in three patients with epileptic encephalopathy due to the recurrent c.320A>G variant in ALG13, characterized to date only in about 60 individuals (mostly female). This is an important preliminary step in the understanding of the pathogenesis of the disease associated with this variant in the rare genetic condition. The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein. Despite this, protein electrophoresis, which is abnormal in most conditions due to abnormalities in N-glycosylation, has been normal or only mildly abnormal in the ALG13 patients. Methods: Nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate and univariate modelling were used to analyze the metabolic profile of the blood serum samples acquired from the studied patients. Results: Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine. Conclusions: Since presented data are the first to be collected so far, they need be verified in further studies. Our intention was to turn attention toward possible CDG-ALG13 laboratory markers that would have clinical significance. MDPI 2021-03-23 /pmc/articles/PMC8004727/ /pubmed/33807002 http://dx.doi.org/10.3390/children8030251 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Paprocka, Justyna
Jezela-Stanek, Aleksandra
Boguszewicz, Łukasz
Sokół, Maria
Lipiński, Patryk
Jamroz, Ewa
Emich-Widera, Ewa
Tylki-Szymańska, Anna
The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant
title The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant
title_full The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant
title_fullStr The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant
title_full_unstemmed The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant
title_short The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant
title_sort first metabolome analysis in children with epilepsy and alg13-cdg resulting from c.320a>g variant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004727/
https://www.ncbi.nlm.nih.gov/pubmed/33807002
http://dx.doi.org/10.3390/children8030251
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