ORAL D-GALACTOSE SUPPLEMENTATION IN PGM1-CDG
| Autor: | Miao He, Jozef Hertecant, Jolanta Sykut-Cegielska, Nurulamin Abu Bakar, Sunnie Yan Wai Wong, Francis Bowling, David Nguyen, Stefanie Perez, Tim L. Emmerzaal, Katja S. Brocke Holmefjord, Jaak Jaeken, Kea Crivelly, Gernot Poschet, Dieter Koch, Amanda M. Ackermann, Eva Morava, François Foulquier, Dirk Lefeber, Hana Hansikova, Nicole Peeters, Marit Mork, K. Michael Gibson, Kimiyo Raymond, Therese Gadomski, Graeme Preston, Christian Thiel, Monique van Scherpenzeel, Tomas Honzik, Tamas Kozicz |
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| Přispěvatelé: | Tulane University, Radboud University Medical Center [Nijmegen], First Faculty of Medicine Charles University [Prague], University of Stavanger, University Hospitals Leuven [Leuven], Washington State University (WSU), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose Male D-galactose Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] Mannose Administration Oral Pilot Projects N-glycosylation glycomics chemistry.chemical_compound Prospective Studies Child Creatine Kinase Genetics (clinical) Skin chemistry.chemical_classification O-glycosylation biology medicine.diagnostic_test Transferrin Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] Glycogen Storage Disease 3. Good health [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry liver function Child Preschool Administration Female Drug Partial thromboplastin time Oral medicine.medical_specialty Glycosylation endocrine LLO Adolescent Antithrombin III Aspartate transaminase Neurophysiology phosphoglucomutase 1 Article Dose-Response Relationship 03 medical and health sciences Young Adult Internal medicine PGM1 medicine Humans coagulation Adverse effect Preschool Blood Coagulation Glycoproteins Dose-Response Relationship Drug business.industry Galactose Infant carbohydrates (lipids) 030104 developmental biology Endocrinology Alanine transaminase chemistry Phosphoglucomutase biology.protein Glycoprotein transferrin glycoforms business |
| Zdroj: | Genetics in medicine : official journal of the American College of Medical Genetics Genetics in Medicine Genetics in Medicine, 2017, Genetics in Medicine. Official Journal of the American College of Medical Genetics, 19 (11), pp.1226-1235. ⟨10.1038/gim.2017.41⟩ Genetics in Medicine, 19, 11, pp. 1226-1235 Genetics in Medicine, 19, 1226-1235 |
| ISSN: | 1530-0366 1098-3600 |
| Popis: | Contains fulltext : 181642.pdf (Publisher’s version ) (Closed access) 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. |
| Databáze: | OpenAIRE |
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