Oral D-galactose supplementation in PGM1-CDG
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Oral D-galactose supplementation in PGM1-CDG
Auteur(s) :
Wong, Sunnie [Auteur]
Tulane University
Gadomski, Therese [Auteur]
Tulane University
van Scherpenzeel, Monique [Auteur]
Radboud University Medical Center [Nijmegen]
Honzik, Tomas [Auteur]
Hansikova, Hana [Auteur]
Holmefjord, Katja S. Brocke [Auteur]
University of Stavanger
Mork, Marit [Auteur]
University of Stavanger
Bowling, Francis [Auteur]
Sykut-Cegielska, Jolanta [Auteur]
Koch, Dieter [Auteur]
Hertecant, Jozef [Auteur]
Preston, Graeme [Auteur]
Tulane University
Jaeken, Jaak [Auteur]
University Hospitals Leuven [Leuven]
Peeters, Nicole [Auteur]
Tulane University
Perez, Stefanie [Auteur]
Tulane University
Nguyen, David Do [Auteur]
Tulane University
Crivelly, Kea [Auteur]
Tulane University
Emmerzaal, Tim [Auteur]
Radboud University Medical Center [Nijmegen]
Gibson, K. Michael [Auteur]
Washington State University [WSU]
Raymond, Kimiyo [Auteur]
Abu Bakar, Nurulamin [Auteur]
Radboud University Medical Center [Nijmegen]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Poschet, Gernot [Auteur]
Ackermann, Amanda M. [Auteur]
He, Miao [Auteur]
Lefeber, Dirk J. [Auteur]
Radboud University Medical Center [Nijmegen]
Thiel, Christian [Auteur]
Kozicz, Tamas [Auteur]
Tulane University
Morava, Eva [Auteur]
Tulane University
Tulane University
Gadomski, Therese [Auteur]
Tulane University
van Scherpenzeel, Monique [Auteur]
Radboud University Medical Center [Nijmegen]
Honzik, Tomas [Auteur]
Hansikova, Hana [Auteur]
Holmefjord, Katja S. Brocke [Auteur]
University of Stavanger
Mork, Marit [Auteur]
University of Stavanger
Bowling, Francis [Auteur]
Sykut-Cegielska, Jolanta [Auteur]
Koch, Dieter [Auteur]
Hertecant, Jozef [Auteur]
Preston, Graeme [Auteur]
Tulane University
Jaeken, Jaak [Auteur]
University Hospitals Leuven [Leuven]
Peeters, Nicole [Auteur]
Tulane University
Perez, Stefanie [Auteur]
Tulane University
Nguyen, David Do [Auteur]
Tulane University
Crivelly, Kea [Auteur]
Tulane University
Emmerzaal, Tim [Auteur]
Radboud University Medical Center [Nijmegen]
Gibson, K. Michael [Auteur]
Washington State University [WSU]
Raymond, Kimiyo [Auteur]
Abu Bakar, Nurulamin [Auteur]
Radboud University Medical Center [Nijmegen]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Poschet, Gernot [Auteur]
Ackermann, Amanda M. [Auteur]
He, Miao [Auteur]
Lefeber, Dirk J. [Auteur]
Radboud University Medical Center [Nijmegen]
Thiel, Christian [Auteur]
Kozicz, Tamas [Auteur]
Tulane University
Morava, Eva [Auteur]
Tulane University
Titre de la revue :
Genetics in Medicine. Official Journal of the American College of Medical Genetics
Nom court de la revue :
Genet. Med.
Numéro :
19
Pagination :
1226-1235
Date de publication :
2017-11
ISSN :
1530-0366
Mot(s)-clé(s) en anglais :
Creatine Kinase
Transferrin
Prospective Studies
Administration, Oral
Humans
Glycoprotein
Child, Preschool
Male
Infant
Blood Glucose
Phosphoglucomutase
Dose-Response Relationship, Drug
Young Adult
Pilot Projects
Adolescent
Blood Coagulation
Female
Skin
Galactose
Child
Glycogen Storage Disease
Transferrin
Prospective Studies
Administration, Oral
Humans
Glycoprotein
Child, Preschool
Male
Infant
Blood Glucose
Phosphoglucomutase
Dose-Response Relationship, Drug
Young Adult
Pilot Projects
Adolescent
Blood Coagulation
Female
Skin
Galactose
Child
Glycogen Storage Disease
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
PurposePhosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous casereports in PGM1-CDG patients receiving oral D-galactose (D-gal) showed clinical improvement. So far no ...
Lire la suite >PurposePhosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous casereports in PGM1-CDG patients receiving oral D-galactose (D-gal) showed clinical improvement. So far no systematic in vitro and clinical studies have assessed safety and benefits of D-gal supplementation. In a prospective pilot study, we evaluated the effects of oral D-gal in nine patients.MethodsD-gal supplementation was increased to 1.5 g/kg/day (maximum 50 g/day) in three increments over 18 weeks. Laboratory studies were performed before and during treatment to monitor safety and effect on serum transferrin-glycosylation, coagulation, and liver and endocrine function. Additionally, the effect of D-gal on cellular glycosylation was characterized in vitro.ResultsEight patients were compliant with D-gal supplementation. No adverse effects were reported. Abnormal baseline results (alanine transaminase, aspartate transaminase, activated partial thromboplastin time) improved or normalized already using 1 g/kg/day D-gal. Antithrombin-III levels and transferrin-glycosylation showed significant improvement, and increase in galactosylation and whole glycan content. In vitro studies before treatment showed N-glycan hyposialylation, altered O-linked glycans, abnormal lipid-linked oligosaccharide profile, and abnormal nucleotide sugars in patient fibroblasts. Most cellular abnormalities improved or normalized following D-gal treatment. D-gal increased both UDP-Glc and UDP-Gal levels and improved lipid-linked oligosaccharide fractions in concert with improved glycosylation in PGM1-CDG.ConclusionOral D-gal supplementation is a safe and effective treatment for PGM1-CDG in this pilot study. Transferrin glycosylation and ATIII levels were useful trial end points. Larger, longer-duration trials are ongoing.Lire moins >
Lire la suite >PurposePhosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous casereports in PGM1-CDG patients receiving oral D-galactose (D-gal) showed clinical improvement. So far no systematic in vitro and clinical studies have assessed safety and benefits of D-gal supplementation. In a prospective pilot study, we evaluated the effects of oral D-gal in nine patients.MethodsD-gal supplementation was increased to 1.5 g/kg/day (maximum 50 g/day) in three increments over 18 weeks. Laboratory studies were performed before and during treatment to monitor safety and effect on serum transferrin-glycosylation, coagulation, and liver and endocrine function. Additionally, the effect of D-gal on cellular glycosylation was characterized in vitro.ResultsEight patients were compliant with D-gal supplementation. No adverse effects were reported. Abnormal baseline results (alanine transaminase, aspartate transaminase, activated partial thromboplastin time) improved or normalized already using 1 g/kg/day D-gal. Antithrombin-III levels and transferrin-glycosylation showed significant improvement, and increase in galactosylation and whole glycan content. In vitro studies before treatment showed N-glycan hyposialylation, altered O-linked glycans, abnormal lipid-linked oligosaccharide profile, and abnormal nucleotide sugars in patient fibroblasts. Most cellular abnormalities improved or normalized following D-gal treatment. D-gal increased both UDP-Glc and UDP-Gal levels and improved lipid-linked oligosaccharide fractions in concert with improved glycosylation in PGM1-CDG.ConclusionOral D-gal supplementation is a safe and effective treatment for PGM1-CDG in this pilot study. Transferrin glycosylation and ATIII levels were useful trial end points. Larger, longer-duration trials are ongoing.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
Mécanismes moléculaires de la N-glycosylation et pathologies associées
Date de dépôt :
2020-02-12T15:11:54Z
2021-03-19T12:18:44Z
2021-03-19T12:18:44Z