title: Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: a pilot study.
abstract: BACKGROUND
  Early occurrence of small-fibre neuropathy (SFN) is a common feature of Fabry disease (FD) - an X-linked storage disorder caused by reduced activity of the α-galactosidase A (α-GAL). Although SFN may result from different disorders, the cause is often unclear. Therefore, we investigated the frequency of FD in patients with SFN of unknown aetiology.
  
  
  METHODS
  Patients with idiopathic SFN, established by sensory quantitative testing and/or skin biopsy, were examined for mutations in the α-GAL gene. Where mutations in the α-GAL gene were identified, levels of globotriaosylceramide (Gb(3)) were measured in urine and blood and the α-GAL activity was evaluated. When new mutations were detected, a diagnostic work-up was performed as well as a Gb(3) accumulation in the skin, lyso-Gb(3) in blood and Gb(3)_24 in urine were proved.
  
  
  RESULTS
  Twenty-four of 29 eligible patients were enrolled in the study. Mutations in the α-GAL gene were observed in five patients. A typical mutation for FD (c.424T>C, [C142R]) was detected in one patient. In four patients, a complex intronic haplotype within the α-GAL gene (IVS0-10C>T [rs2071225], IVS4-16A>G [rs2071397], IVS6-22C>T [rs2071228]) was identified. The relevance of this haplotype in the pathogenesis of FD remains unclear until now. However, these patients showed increased concentrations of Gb(3) and/or lyso-Gb(3), while no further manifestations for FD could be proved.
  
  
  CONCLUSIONS
  Fabry disease should be considered in patients with SFN of unknown aetiology, and screening for FD should be included in the diagnostic guidelines for SFN. The significance of the intronic haplotype regarding SFN needs further evaluation.
authors.affiliation: Department of Neurology, Justus Liebig University, Giessen, Germany. christian.tanislav@neuro.med.uni-giessen.de
authors.forename: C
authors.initials: C
authors.lastname: Tanislav
authors.forename: M
authors.initials: M
authors.lastname: Kaps
authors.forename: A
authors.initials: A
authors.lastname: Rolfs
authors.forename: T
authors.initials: T
authors.lastname: Böttcher
authors.forename: K
authors.initials: K
authors.lastname: Lackner
authors.forename: E
authors.initials: E
authors.lastname: Paschke
authors.forename: H
authors.initials: H
authors.lastname: Mascher
authors.forename: M
authors.initials: M
authors.lastname: Laue
authors.forename: F
authors.initials: F
authors.lastname: Blaes
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000150:complications* / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009154:Mutation; D010865:Pilot Projects; D011115:Polyneuropathies / Q000235:genetics*; D000519:alpha-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase