title: Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib.
abstract: Glycogen storage disease type Ib (GSD-Ib) is characterized by impaired glucose homeostasis, neutropenia and neutrophil dysfunction. Mass spectrometric glycomic profiling of GSD-Ib neutrophils showed severely truncated N-glycans, lacking galactose. Experiments indicated the hypoglycosylation of the electron transporting subunit of NADPH oxidase, which is crucial for the defense against bacterial infections. In phosphoglucomutase 1 (PGM1) deficiency, an inherited disorder with an enzymatic defect just one metabolic step ahead, hypogalactosylation can be successfully treated by dietary galactose. We hypothesized the same pathomechanism in GSD-Ib and started a therapeutic trial with oral galactose and uridine. The aim was to improve neutrophil dysfunction through the correction of hypoglycosylation in neutrophils. The GSD-Ib patient was treated for 29weeks. Monitoring included glycomics analysis of the patient's neutrophils and neutrophil function tests including respiratory burst activity, phagocytosis and migration. Although no substantial restoration of neutrophil glycosylation was found, there was partial improvement of respiratory burst activity.
authors.affiliation: Department of General Pediatrics, Metabolic Diseases, University Children's Hospital Muenster, Germany. Electronic address: r.letkemann@uni-muenster.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Letkemann
authors.affiliation: Department of Pediatric Rheumatology and Imunology, University Children's Hospital Muenster, Germany. Electronic address: helmut.wittkowski@ukmuenster.de.
authors.forename: Helmut
authors.initials: H
authors.lastname: Wittkowski
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ, UK. Electronic address: a.antonopoulos@imperial.ac.uk.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Antonopoulos
authors.affiliation: Molecular Genetics and Metabolism Laboratory, Munich, Germany. Electronic address: metabolic-genetic-disease@gmx.de.
authors.forename: Teodor
authors.initials: T
authors.lastname: Podskabi
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ, UK. Electronic address: s.haslam@imperial.ac.uk.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.affiliation: Department of Pediatric Rheumatology and Imunology, University Children's Hospital Muenster, Germany. Electronic address: dfoell@uni-muenster.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Föll
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ, UK. Electronic address: a.dell@imperial.ac.uk.
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.affiliation: Department of General Pediatrics, Metabolic Diseases, University Children's Hospital Muenster, Germany. Electronic address: marquat@uni-muenster.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Marquardt
mesh_terms: D000284:Administration, Oral; D017920:Antiporters / Q000235:genetics*; D005260:Female; D005690:Galactose / Q000627:therapeutic use*; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D005953:Glycogen Storage Disease Type I / Q000188:drug therapy* / Q000235:genetics; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy* / Q000235:genetics; D007223:Infant; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D055815:Young Adult
chemical_list: D017920:Antiporters; D009004:Monosaccharide Transport Proteins; C503531:SLC37A4 protein, human; D019255:NADPH Oxidases; D005947:Glucose; D005690:Galactose
keywords: CDG; Galactose; Glycogen storage disease; Glycosylation; Neutrophil dysfunction