title: A novel GBE1 mutation and features of polyglucosan bodies autophagy in adult polyglucosan body disease.
abstract: We report the clinical, neuro-imaging, pathological and biochemical features of an Italian family in which two siblings have the Adult Polyglucosan Body Disease (APBD). APBD is a rare autosomal recessive disorder characterized by a gradually progressive involvement of both the central and peripheral nervous systems caused by the deficiency of the glycogen branching enzyme (GBE1). The two affected siblings, a 64-year-old man and his 67-year-old sister who had complained of urinary urgency and sporadic incontinence and also progressive gait difficulty for 6 and 7 years respectively, had severely impaired deep sensations on direct examination and a moderately severe symmetrical, axonal sensory-motor neuropathy on electrophysiological testing. GBE1 activity was below 25% of the normal rate in leukocytes and sural nerves. The siblings were homozygous for the novel GBE1 mutation p.N541D. All other members of the pedigree are heterozygous and manifest no symptoms, even in the very elderly. The affected siblings showed polyglucosan bodies (PBs) included within non-myelinating Schwann cells and within lymphocyte vesicles, which were positive for the autophagy markers P62 and LC3-II at immunofluorescence microscopy.
authors.affiliation: Neurology Clinic II, Department of Medical Sciences, Surgery, Neurology, Metabolic Diseases and Geriatrics, Second University of Naples, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Sampaolo
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council, Naples, Italy. Electronic address: teresa.esposito@igb.cnr.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Esposito
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council, Naples, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gianfrancesco
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council, Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Napolitano
authors.affiliation: Neurology Clinic II, Department of Medical Sciences, Surgery, Neurology, Metabolic Diseases and Geriatrics, Second University of Naples, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Lombardi
authors.affiliation: Department of Veterinary Medicine and Animal Production, University of Naples "Federico II", Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lucà
authors.affiliation: Department of Veterinary Medicine and Animal Production, University of Naples "Federico II", Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Roperto
authors.affiliation: Neurology Clinic II, Department of Medical Sciences, Surgery, Neurology, Metabolic Diseases and Geriatrics, Second University of Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Iorio
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006008:Glycogen Storage Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010375:Pedigree; D035781:Siblings; D013116:Spinal Cord / Q000473:pathology; D013497:Sural Nerve / Q000473:pathology; D044465:White People / Q000235:genetics
chemical_list: D006004:Glycogen Debranching Enzyme System; C577876:GBE1 protein, human
keywords: Adult Polyglucosan Body Disease (APBD); Autophagy; GBE1 mutation analysis; Glycogen branching enzyme (GBE1); Polyglucosan Bodies in lymphocytes