title: Clinical prodromes of neurodegeneration in Anderson-Fabry disease.
abstract: OBJECTIVE
  To estimate the prevalence of prodromal clinical features of neurodegeneration in patients with Anderson-Fabry disease (AFD) in comparison to age-matched controls.
  
  
  METHODS
  This is a single-center, prospective, cross-sectional study in 167 participants (60 heterozygous females and 50 hemizygous males with genetically confirmed AFD, 57 age-matched controls) using a clinical screening program consisting of structured interview, quantitative tests of motor function, and assessments of cognition, depression, olfaction, orthostatic intolerance, pain, REM sleep behavior disorder, and daytime sleepiness.
  
  
  RESULTS
  In comparison to age-matched controls (mean age 48.3 years), patients with AFD (mean age 49.0 years) showed slower gait and transfer speed, poorer fine manual dexterity, and lower hand speed, which was independent of focal symptoms due to cerebrovascular disease. Patients with AFD were more severely affected by depression, pain, and daytime sleepiness and had a lower quality of life. These motor and nonmotor manifestations significantly correlated with clinical disease severity. However, patients with AFD did not reveal extrapyramidal motor features or signs of significant cognitive impairment, hyposmia, orthostatic intolerance, or REM sleep behavior disorder, which commonly precede later neurodegenerative disease. In our cohort, there were no differences in neurologic manifestations of AFD between heterozygous females and hemizygous males.
  
  
  CONCLUSIONS
  Aside from cerebrovascular manifestations and small fiber neuropathy, AFD results in a distinct neurologic phenotype comprising poorer motor performance and specific nonmotor features. In contrast to functional loss of glucocerebrosidase in Gaucher disease, α-galactosidase deficiency in AFD is not associated with a typical cluster of clinical features prodromal for neurodegenerative diseases, such as Parkinson disease.
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany. matthias.loehle@uniklinikum-dresden.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Löhle
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany.
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany.
authors.forename: Alan
authors.initials: A
authors.lastname: Milligan
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Richfield
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany.
authors.forename: Atul
authors.initials: A
authors.lastname: Mehta
authors.affiliation: From the Department of Clinical Neuroscience, Institute of Neurology (M.L., A.H.V.S.), and the Lysosomal Storage Disorders Unit, Department of Haematology (D.H., A.M., L.R., A.M.), University College London, UK; and the Department of Neurology (M.L., H.R.), Dresden University of Technology, Germany.
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D000795:Fabry Disease / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology*; D010641:Phenotype; D015995:Prevalence; D062706:Prodromal Symptoms; D011446:Prospective Studies; D012720:Severity of Illness Index; D055815:Young Adult