title: Uncertain diagnosis of fabry disease in patients with neuropathic pain, angiokeratoma or cornea verticillata: consensus on the approach to diagnosis and follow-up.
abstract: BACKGROUND
  Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the α-galactosidase A (GLA) gene may be unclear. This uncertainty often leads to considerable distress and inappropriate counselling and treatment. We developed a clinical approach for these individuals with an uncertain diagnosis of FD.
  
  
  METHODS
  A document was presented to an FD expert panel with background information based on clinical experience and the literature, followed by an online survey and a written recommendation.
  
  
  RESULTS
  The 13 experts agreed that the recommendation is intended for individuals with neuropathic pain, AK and/or CV only, i.e. without kidney, heart or brain disease, with an uncertain diagnosis of FD. Only in the presence of FD-specific neuropathic pain (small fibre neuropathy with FD-specific pattern), AK (FD-specific localisations) or CV (without CV inducing medication), FD is confirmed. When these features have a non-specific pattern, there is insufficient evidence for FD. If no alternative diagnosis is found, follow-up is recommended.
  
  
  CONCLUSIONS
  In individuals with an uncertain diagnosis of FD, the presence of an FD-specific pattern of CV, AK or neuropathic pain is sufficient to confirm the diagnosis of FD. When these features are non-specific, a definite diagnosis cannot (yet) be established and follow-up is indicated. ERT should be considered only in those patients with a confirmed diagnosis of FD.
authors.affiliation: Department of Internal Medicine, Division Endocrinology and Metabolism, Amsterdam lysosome centre 'Sphinx', Academic Medical Center, University of Amsterdam, Room F5-166, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van der Tol
authors.forename: David
authors.initials: D
authors.lastname: Cassiman
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houge
authors.forename: Mirian C
authors.initials: MC
authors.lastname: Janssen
authors.forename: Robin H
authors.initials: RH
authors.lastname: Lachmann
authors.forename: Gabor E
authors.initials: GE
authors.lastname: Linthorst
authors.forename: Uma
authors.initials: U
authors.lastname: Ramaswami
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.forename: Camilla
authors.initials: C
authors.lastname: Tøndel
authors.forename: Michael L
authors.initials: ML
authors.lastname: West
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
authors.forename: Carla Em
authors.initials: CE
authors.lastname: Hollak
authors.forename: Marieke
authors.initials: M
authors.lastname: Biegstraaten