Advanced search
1 file | 518.65 KB Add to list
Author
Abstract
Purpose: Phosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous case reports 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. Methods: D-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. Results: Eight 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. Conclusion: Oral 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.
Keywords
coagulation, glycomics, LLO, glycosylation, phosphoglucomutase 1, PHOSPHOGLUCOMUTASE 1 DEFICIENCY, CONGENITAL DISORDERS, MASS-SPECTROMETRY, GLYCOSYLATION, IDENTIFICATION, CDG, PHENOTYPE, DIAGNOSIS, MANNOSE, DEFECTS

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 518.65 KB

Citation

Please use this url to cite or link to this publication:

MLA
Wong, Sunnie Yan-Wai et al. “Oral D-galactose Supplementation in PGM1-CDG.” GENETICS IN MEDICINE 19.11 (2017): 1226–1235. Print.
APA
Wong, S. Y.-W., Gadomski, T., van Scherpenzeel, M., Honzik, T., Hansikova, H., Holmefjord, K. S. B., Mork, M., et al. (2017). Oral D-galactose supplementation in PGM1-CDG. GENETICS IN MEDICINE, 19(11), 1226–1235.
Chicago author-date
Wong, Sunnie Yan-Wai, Therese Gadomski, Monique van Scherpenzeel, Tomas Honzik, Hana Hansikova, Katja S Brocke Holmefjord, Marit Mork, et al. 2017. “Oral D-galactose Supplementation in PGM1-CDG.” Genetics in Medicine 19 (11): 1226–1235.
Chicago author-date (all authors)
Wong, Sunnie Yan-Wai, Therese Gadomski, Monique van Scherpenzeel, Tomas Honzik, Hana Hansikova, Katja S Brocke Holmefjord, Marit Mork, Francis Bowling, Jolanta Sykut-Cegielska, Dieter Koch, Jozef Hertecant, Graeme Preston, Jaak Jaeken, Nicky Peeters, Stefanie Perez, David Do Nguyen, Kea Crivelly, Tim Emmerzaal, K Michael Gibson, Kimiyo Raymond, Nurulamin Abu Bakar, Francois Foulquier, Gernot Poschet, Amanda M Ackermann, Miao He, Dirk J Lefeber, Christian Thiel, Tamas Kozicz, and Eva Morava. 2017. “Oral D-galactose Supplementation in PGM1-CDG.” Genetics in Medicine 19 (11): 1226–1235.
Vancouver
1.
Wong SY-W, Gadomski T, van Scherpenzeel M, Honzik T, Hansikova H, Holmefjord KSB, et al. Oral D-galactose supplementation in PGM1-CDG. GENETICS IN MEDICINE. 2017;19(11):1226–35.
IEEE
[1]
S. Y.-W. Wong et al., “Oral D-galactose supplementation in PGM1-CDG,” GENETICS IN MEDICINE, vol. 19, no. 11, pp. 1226–1235, 2017.
@article{8580208,
  abstract     = {Purpose: Phosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous case reports 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. 
Methods: D-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. 
Results: Eight 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. 
Conclusion: Oral 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.},
  author       = {Wong, Sunnie Yan-Wai and Gadomski, Therese and van Scherpenzeel, Monique and Honzik, Tomas and Hansikova, Hana and Holmefjord, Katja S Brocke and Mork, Marit and Bowling, Francis and Sykut-Cegielska, Jolanta and Koch, Dieter and Hertecant, Jozef and Preston, Graeme and Jaeken, Jaak and Peeters, Nicky and Perez, Stefanie and Nguyen, David Do and Crivelly, Kea and Emmerzaal, Tim and Gibson, K Michael and Raymond, Kimiyo and Abu Bakar, Nurulamin and Foulquier, Francois and Poschet, Gernot and Ackermann, Amanda M and He, Miao and Lefeber, Dirk J and Thiel, Christian and Kozicz, Tamas and Morava, Eva},
  issn         = {1098-3600},
  journal      = {GENETICS IN MEDICINE},
  keywords     = {coagulation,glycomics,LLO,glycosylation,phosphoglucomutase 1,PHOSPHOGLUCOMUTASE 1 DEFICIENCY,CONGENITAL DISORDERS,MASS-SPECTROMETRY,GLYCOSYLATION,IDENTIFICATION,CDG,PHENOTYPE,DIAGNOSIS,MANNOSE,DEFECTS},
  language     = {eng},
  number       = {11},
  pages        = {1226--1235},
  title        = {Oral D-galactose supplementation in PGM1-CDG},
  url          = {http://dx.doi.org/10.1038/gim.2017.41},
  volume       = {19},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: