title: No Fabry Disease in Patients Presenting with Isolated Small Fiber Neuropathy.
abstract: OBJECTIVE
  Screening for Fabry disease in patients with small fiber neuropathy has been suggested, especially since Fabry disease is potentially treatable. However, the diagnostic yield of testing for Fabry disease in isolated small fiber neuropathy patients has never been systematically investigated. Our aim is to determine the presence of Fabry disease in patients with small fiber neuropathy.
  
  
  METHODS
  Patients referred to our institute, who met the criteria for isolated small fiber neuropathy were tested for Fabry disease by measurement of alpha-Galactosidase A activity in blood, lysosomal globotriaosylsphingosine in urine and analysis on possible GLA gene mutations.
  
  
  RESULTS
  725 patients diagnosed with small fiber neuropathy were screened for Fabry disease. No skin abnormalities were seen except for redness of the hands or feet in 30.9% of the patients. Alfa-Galactosidase A activity was tested in all 725 patients and showed diminished activity in eight patients. Lysosomal globotriaosylsphingosine was examined in 509 patients and was normal in all tested individuals. Screening of GLA for mutations was performed for 440 patients, including those with diminished α-Galactosidase A activity. Thirteen patients showed a GLA gene variant. One likely pathogenic variant was found in a female patient. The diagnosis Fabry disease could not be confirmed over time in this patient. Eventually none of the patients were diagnosed with Fabry disease.
  
  
  CONCLUSIONS
  In patients with isolated small fiber neuropathy, and no other signs compatible with Fabry disease, the diagnostic yield of testing for Fabry disease is extremely low. Testing for Fabry disease should be considered only in cases with additional characteristics, such as childhood onset, cardiovascular disease, renal failure, or typical skin lesions.
authors: Department of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Bianca T A
authors: BT
authors: de Greef
authors: Department of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Janneke G J
authors: JG
authors: Hoeijmakers
authors: Department of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Emma E
authors: EE
authors: Wolters
authors: Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Hubertus J M
authors: HJ
authors: Smeets
authors: Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Arthur
authors: A
authors: van den Wijngaard
authors: Department of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of Neurology, Spaarne hospital, Hoofddorp, The Netherlands.
authors: Ingemar S J
authors: IS
authors: Merkies
authors: Department of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Catharina G
authors: CG
authors: Faber
authors: Department of Neurology, Spaarne hospital, Hoofddorp, The Netherlands.
authors: Monique M
authors: MM
authors: Gerrits
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006017:Glycolipids / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D009422:Nervous System Diseases / Q000150:complications*; D009437:Neuralgia / Q000150:complications; D015995:Prevalence; D012189:Retrospective Studies; D012678:Sensation Disorders / Q000150:complications; D017422:Sequence Analysis, DNA; D013107:Sphingolipids / Q000652:urine*; D055815:Young Adult; D000519:alpha-Galactosidase / Q000097:blood* / Q000235:genetics
chemical_list: D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; C576330:GLA protein, human; D000519:alpha-Galactosidase