title: In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease.
abstract: BACKGROUND
  Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an α-galactosidase A enzyme deficiency due to pathogenic variants in the α-galactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite diagnosis of FD has important consequences for treatment and counselling.
  
  
  OBJECTIVE
  We assessed the diagnostic value of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) for patients with an uncertain FD diagnosis.
  
  
  METHODS
  All patients with a GLA variant who initially presented at the Academic Medical Center with an uncertain FD diagnosis were included. A biopsy of an affected organ in a patient or family member showing FD characteristic storage is used as a reference standard for a diagnosis of FD. All patients underwent a comprehensive QST protocol and IENFD assessment which was compared to age and gender-matched healthy controls. Sensitivity and specificity were calculated for a combination of ≥1 abnormal QST modality and an abnormal IENFD.
  
  
  RESULTS
  Twenty-six patients participated (nonclassical FD n = 18, 9 males; no FD n = 5, 3 males; uncertain n = 3, 1 male). Of the patients classified as nonclassical FD, 28% had ≥1 abnormal QST modalities, and 83% had an abnormal IENFD. From the patients without FD, 20% had ≥1 abnormal QST modality, and IENFD was abnormal in 25% (1 not available). Sensitivity was 28% and specificity 80%.
  
  
  CONCLUSIONS
  In our study cohort, QST and IENFD could not reliably distinguish patients with FD from those without FD.
authors.affiliation: Department of Endocrinology and Metabolism, Amsterdam lysosome center 'Sphinx', Amsterdam, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: van der Tol
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Camiel
authors.initials: C
authors.lastname: Verhamme
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ivo N
authors.initials: IN
authors.lastname: van Schaik
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.affiliation: Department of Endocrinology and Metabolism, Amsterdam lysosome center 'Sphinx', Amsterdam, The Netherlands.
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
authors.affiliation: Department of Endocrinology and Metabolism, Amsterdam lysosome center 'Sphinx', Amsterdam, The Netherlands. M.Biegstraaten@amc.uva.nl.|Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Room F5-166, Meibergdreef 9, 1105, Amsterdam, The Netherlands. M.Biegstraaten@amc.uva.nl.
authors.forename: Marieke
authors.initials: M
authors.lastname: Biegstraaten