Arnaud Bruneel1, Sophie Cholet2, N Thuy Tran3, Thanh Duc Mai3, François Fenaille4. 1. AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France; Université Paris-Saclay, INSERM UMR1193, Mécanismes cellulaires et moléculaires de l'adaptation au stress et cancérogenèse, Châtenay-Malabry, France. Electronic address: arnaud.bruneel@aphp.fr. 2. Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, F-91191 Gif sur Yvette, France. 3. Université Paris-Saclay, CNRS, Institut Galien Paris Saclay, Châtenay-Malabry, France. 4. Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, F-91191 Gif sur Yvette, France. Electronic address: francois.fenaille@cea.fr.
Abstract
BACKGROUND: Glycosylation is one of the most complex post-translational modifications of proteins and lipids, notably requiring many glycosyltransferases, glycosidases and sugar transporters encoded by about 1-2% of all human genes. Deleterious variants in any of them may result in improper protein or lipid glycosylation, thus yielding the so-called 'congenital disorders of glycosylation' or CDG. SCOPE OF REVIEW: We first review the current state of knowledge on the common blood and cellular glycoproteins used in the biochemical screening of CDG, as well as the emerging ones for an improved diagnosis. We then provide an overview of the current state-of-the-art methodologies ranging from gel electrophoresis to mass spectrometry to measure improper glycosylation. Finally, we discuss how additional tools such as metabolomics and microfluidics can be added to the current toolbox to better diagnose and delineate CDG. MAJOR CONCLUSIONS: Combining several biochemical indicators and related methods is often required to cope with the large clinical heterogeneity of CDG and establish a definitive diagnosis. GENERAL SIGNIFICANCE: This review aims to critically present current available CDG biochemical biomarkers and dedicated methods in the context of highly diverse glycosylation pathways and related inherited diseases.
BACKGROUND: Glycosylation is one of the most complex post-translational modifications of proteins and lipids, notably requiring many glycosyltransferases, glycosidases and sugar transporters encoded by about 1-2% of all human genes. Deleterious variants in any of them may result in improper protein or lipid glycosylation, thus yielding the so-called 'congenital disorders of glycosylation' or CDG. SCOPE OF REVIEW: We first review the current state of knowledge on the common blood and cellular glycoproteins used in the biochemical screening of CDG, as well as the emerging ones for an improved diagnosis. We then provide an overview of the current state-of-the-art methodologies ranging from gel electrophoresis to mass spectrometry to measure improper glycosylation. Finally, we discuss how additional tools such as metabolomics and microfluidics can be added to the current toolbox to better diagnose and delineate CDG. MAJOR CONCLUSIONS: Combining several biochemical indicators and related methods is often required to cope with the large clinical heterogeneity of CDG and establish a definitive diagnosis. GENERAL SIGNIFICANCE: This review aims to critically present current available CDG biochemical biomarkers and dedicated methods in the context of highly diverse glycosylation pathways and related inherited diseases.
Authors: Rita Francisco; Sandra Brasil; Carlota Pascoal; Andrew C Edmondson; Jaak Jaeken; Paula A Videira; Cláudia de Freitas; Vanessa Dos Reis Ferreira; Dorinda Marques-da-Silva Journal: Int J Environ Res Public Health Date: 2022-06-02 Impact factor: 4.614