Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Oral D-galactose supplementation in PGM1-CDG

SY. Wong, T. Gadomski, M. van Scherpenzeel, T. Honzik, H. Hansikova, KSB. Holmefjord, M. Mork, F. Bowling, J. Sykut-Cegielska, D. Koch, J. Hertecant, G. Preston, J. Jaeken, N. Peeters, S. Perez, DD. Nguyen, K. Crivelly, T. Emmerzaal, KM. Gibson,...

. 2017 ; 19 (11) : 1226-1235. [pub] 20170615

Language English Country United States

Document type Clinical Trial, Journal Article

Persistent link   https://www.medvik.cz/link/bmc18024939

Grant support
NV16-31932A MZ0 CEP Register

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.

Biochemical Diseases Mater Children's Hospital South Brisbane Queensland Australia

Center for Child and Adolescent Medicine Kinderheilkunde 1 University of Heidelberg Heidelberg Germany

Centre for Organismal Studies University of Heidelberg Heidelberg Germany

Department of Anatomy Radboud University Medical Centre Nijmegen The Netherlands

Department of Neurology Translational Metabolic Laboratory Donders Institute for Brain Cognition and Behavior Radboudumc Nijmegen The Netherlands

Department of Pediatric Habilitation Stavanger University Hospital Stavanger Norway

Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

Department of Pediatrics University Hospitals Leuven Leuven Belgium

Division of Endocrinology and Diabetes The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

Division of Laboratory Genetics Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA

Genetics Metabolics Service Tawam Hospital Al Ain United Arab Emirates

Hayward Genetics Center Tulane University School of Medicine New Orleans Louisiana USA

Hayward Genetics Center Tulane University School of Medicine New Orleans Louisiana USA Department of Anatomy Radboud University Medical Centre Nijmegen The Netherlands

Palmieri Metabolic Disease Laboratory The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

Pediatric Cardiology Bergisch Gladbacher Koln Koln Germany

Screening and Metabolic Diagnostics Department The Institute of Mother and Child Warsaw Poland

University Lille CNRS UMR 8576 UGSF Unité de Glycobiologie Structurale et Fonctionnelle Lille France

Washington State University College of Pharmacy Spokane Washington USA

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18024939
003      
CZ-PrNML
005      
20180716094750.0
007      
ta
008      
180709s2017 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1038/gim.2017.41 $2 doi
035    __
$a (PubMed)28617415
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Wong, Sunnie Yan-Wai $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
245    10
$a Oral D-galactose supplementation in PGM1-CDG / $c SY. Wong, T. Gadomski, M. van Scherpenzeel, T. Honzik, H. Hansikova, KSB. Holmefjord, M. Mork, F. Bowling, J. Sykut-Cegielska, D. Koch, J. Hertecant, G. Preston, J. Jaeken, N. Peeters, S. Perez, DD. Nguyen, K. Crivelly, T. Emmerzaal, KM. Gibson, K. Raymond, N. Abu Bakar, F. Foulquier, G. Poschet, AM. Ackermann, M. He, DJ. Lefeber, C. Thiel, T. Kozicz, E. Morava,
520    9_
$a 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.
650    _2
$a aplikace orální $7 D000284
650    _2
$a mladiství $7 D000293
650    _2
$a hemokoagulace $7 D001777
650    _2
$a krevní glukóza $x metabolismus $7 D001786
650    _2
$a dítě $7 D002648
650    _2
$a předškolní dítě $7 D002675
650    _2
$a kreatinkinasa $x krev $7 D003402
650    _2
$a vztah mezi dávkou a účinkem léčiva $7 D004305
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a galaktosa $x aplikace a dávkování $x škodlivé účinky $x terapeutické užití $7 D005690
650    _2
$a glykogenóza $x farmakoterapie $7 D006008
650    _2
$a glykoproteiny $x metabolismus $7 D006023
650    _2
$a lidé $7 D006801
650    _2
$a kojenec $7 D007223
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a fosfoglukomutasa $x metabolismus $7 D010733
650    _2
$a pilotní projekty $7 D010865
650    _2
$a prospektivní studie $7 D011446
650    _2
$a kůže $x cytologie $x metabolismus $7 D012867
650    _2
$a transferin $x metabolismus $7 D014168
650    _2
$a mladý dospělý $7 D055815
655    _2
$a klinické zkoušky $7 D016430
655    _2
$a časopisecké články $7 D016428
700    1_
$a Gadomski, Therese $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
700    1_
$a van Scherpenzeel, Monique $u Department of Neurology, Translational Metabolic Laboratory, Donders Institute for Brain, Cognition, and Behavior, Radboudumc, Nijmegen, The Netherlands.
700    1_
$a Honzik, Tomas $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Hansikova, Hana $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Holmefjord, Katja S Brocke $u Department of Pediatric Habilitation, Stavanger University Hospital, Stavanger, Norway.
700    1_
$a Mork, Marit $u Department of Pediatric Habilitation, Stavanger University Hospital, Stavanger, Norway.
700    1_
$a Bowling, Francis $u Biochemical Diseases, Mater Children's Hospital, South, Brisbane, Queensland, Australia.
700    1_
$a Sykut-Cegielska, Jolanta $u Screening and Metabolic Diagnostics Department, The Institute of Mother and Child, Warsaw, Poland.
700    1_
$a Koch, Dieter $u Pediatric Cardiology, Bergisch Gladbacher Koln, Koln, Germany.
700    1_
$a Hertecant, Jozef $u Genetics/Metabolics Service, Tawam Hospital, Al Ain, United Arab Emirates.
700    1_
$a Preston, Graeme $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
700    1_
$a Jaeken, Jaak $u Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
700    1_
$a Peeters, Nicole $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
700    1_
$a Perez, Stefanie $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
700    1_
$a Nguyen, David Do $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
700    1_
$a Crivelly, Kea $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
700    1_
$a Emmerzaal, Tim $u Department of Anatomy, Radboud University Medical Centre, Nijmegen, The Netherlands.
700    1_
$a Gibson, K Michael $u Washington State University College of Pharmacy, Spokane, Washington, USA.
700    1_
$a Raymond, Kimiyo $u Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
700    1_
$a Abu Bakar, Nurulamin $u Department of Neurology, Translational Metabolic Laboratory, Donders Institute for Brain, Cognition, and Behavior, Radboudumc, Nijmegen, The Netherlands.
700    1_
$a Foulquier, Francois $u University Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
700    1_
$a Poschet, Gernot $u Centre for Organismal Studies (COS), University of Heidelberg, Heidelberg, Germany.
700    1_
$a Ackermann, Amanda M $u Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
700    1_
$a He, Miao $u Palmieri Metabolic Disease Laboratory, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
700    1_
$a Lefeber, Dirk J $u Department of Neurology, Translational Metabolic Laboratory, Donders Institute for Brain, Cognition, and Behavior, Radboudumc, Nijmegen, The Netherlands.
700    1_
$a Thiel, Christian $u Center for Child and Adolescent Medicine, Kinderheilkunde I, University of Heidelberg, Heidelberg, Germany.
700    1_
$a Kozicz, Tamas $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA. Department of Anatomy, Radboud University Medical Centre, Nijmegen, The Netherlands.
700    1_
$a Morava, Eva $u Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
773    0_
$w MED00186213 $t Genetics in medicine official journal of the American College of Medical Genetics $x 1530-0366 $g Roč. 19, č. 11 (2017), s. 1226-1235
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28617415 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180709 $b ABA008
991    __
$a 20180716095048 $b ABA008
999    __
$a ok $b bmc $g 1317070 $s 1021860
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 19 $c 11 $d 1226-1235 $e 20170615 $i 1530-0366 $m Genetics in medicine $n Genet Med $x MED00186213
GRA    __
$a NV16-31932A $p MZ0
LZP    __
$a Pubmed-20180709
Back

Find record

Citation metrics

Archiving options