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Genet Med. 2017 Nov;19(11):1226-1235. doi: 10.1038/gim.2017.41. Epub 2017 Jun 15.

Oral D-galactose supplementation in PGM1-CDG.

Author information

1
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
2
Department of Neurology, Translational Metabolic Laboratory, Donders Institute for Brain, Cognition, and Behavior, Radboudumc, Nijmegen, The Netherlands.
3
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
4
Department of Pediatric Habilitation, Stavanger University Hospital, Stavanger, Norway.
5
Biochemical Diseases, Mater Children's Hospital, South, Brisbane, Queensland, Australia.
6
Screening and Metabolic Diagnostics Department, The Institute of Mother and Child, Warsaw, Poland.
7
Pediatric Cardiology, Bergisch Gladbacher Koln, Koln, Germany.
8
Genetics/Metabolics Service, Tawam Hospital, Al Ain, United Arab Emirates.
9
Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
10
Department of Anatomy, Radboud University Medical Centre, Nijmegen, The Netherlands.
11
Washington State University College of Pharmacy, Spokane, Washington, USA.
12
Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
13
University Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
14
Centre for Organismal Studies (COS), University of Heidelberg, Heidelberg, Germany.
15
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
16
Palmieri Metabolic Disease Laboratory, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
17
Center for Child and Adolescent Medicine, Kinderheilkunde I, University of Heidelberg, Heidelberg, Germany.

Abstract

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.

PMID:
28617415
PMCID:
PMC5675745
DOI:
10.1038/gim.2017.41
[Indexed for MEDLINE]
Free PMC Article

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