title: Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings.
abstract: OBJECTIVE
  Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD.
  
  
  METHODS
  We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients.
  
  
  RESULTS
  The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation.
  
  
  CONCLUSIONS
  APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy.
authors.affiliation: French Institute of Health and Medical Research, UMR S975, Paris, Frane. fanny.mochel@upmc.fr
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Marjan E
authors.initials: ME
authors.lastname: Steenweg
authors.forename: Hasan O
authors.initials: HO
authors.lastname: Akman
authors.forename: Mary
authors.initials: M
authors.lastname: Wallace
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sedel
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.forename: Richard
authors.initials: R
authors.lastname: Levy
authors.forename: J Michael
authors.initials: JM
authors.lastname: Powers
authors.forename: Sophie
authors.initials: S
authors.lastname: Demeret
authors.forename: Thierry
authors.initials: T
authors.lastname: Maisonobe
authors.forename: Roseline
authors.initials: R
authors.lastname: Froissart
authors.forename: Bruno Barcelos
authors.initials: BB
authors.lastname: Da Nobrega
authors.forename: Brent L
authors.initials: BL
authors.lastname: Fogel
authors.forename: Marvin R
authors.initials: MR
authors.lastname: Natowicz
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenmann
authors.forename: Varda
authors.initials: V
authors.lastname: Barash
authors.forename: Or
authors.initials: O
authors.lastname: Kakhlon
authors.forename: J Moshe
authors.initials: JM
authors.lastname: Gomori
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
mesh_terms: D015061:1,4-alpha-Glucan Branching Enzyme / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D005602:France; D006008:Glycogen Storage Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007557:Israel; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009426:Netherlands; D009460:Neurologic Examination; D013116:Spinal Cord / Q000473:pathology; D014481:United States
chemical_list: D015061:1,4-alpha-Glucan Branching Enzyme