title: Cornea verticillata supports a diagnosis of Fabry disease in non-classical phenotypes: results from the Dutch cohort and a systematic review.
abstract: BACKGROUND
  Screening for Fabry disease (FD) increasingly reveals individuals without characteristic features and with a variant of unknown significance in the α-galactosidase A (GLA) gene. Cornea verticillata (CV) assessment, as a characteristic sign of FD, may be a valuable diagnostic tool to assess whether these individuals have a non-classical phenotype or no FD at all.
  
  
  METHODS
  We performed a systematic review to estimate the prevalence of CV in FD. Additionally, CV prevalence was assessed in the Dutch FD cohort. Data were stratified by gender and phenotype (classical, non-classical, uncertain, no-FD) using predefined criteria.
  
  
  RESULTS
  CV was assessed in 21 cohorts (n=753, 330 men, age 0-85 years). Pooled prevalence was 69% (74% men, 66% women). In six studies, 77 (19 men) individuals with a non-classical or uncertain diagnosis were identified. Individual data were available in 4/6 studies (n=66, 16 men). CV was present in 24% (n=16, 2 men). 101 (35 men) subjects from the Dutch cohort were grouped as classical, of whom 86% (94% men, 82% women including five women who used amiodarone) had CV. Of the 25 (11 men) non-classical patients, 4 (three men) had CV. Subjects in the uncertain and no-FD groups did not have CV.
  
  
  CONCLUSIONS
  CV is related to classical or biopsy-proven non-classical FD, with a very high sensitivity in classical men. Thus, presence of CV in an individual with an uncertain diagnosis of FD indicates a pathogenic GLA variant, in the absence of medication that may induce CV; if CV is absent, FD cannot be excluded.
authors: Department of Endocrinology and Metabolism, Amsterdam Lysosome Center 'Sphinx', Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Linda
authors: L
authors: van der Tol
authors: Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Ophthalmology, Medical Center Alkmaar, Alkmaar, The Netherlands.
authors: Marije L
authors: ML
authors: Sminia
authors: Department of Endocrinology and Metabolism, Amsterdam Lysosome Center 'Sphinx', Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Carla E M
authors: CE
authors: Hollak
authors: Department of Endocrinology and Metabolism, Amsterdam Lysosome Center 'Sphinx', Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Marieke
authors: M
authors: Biegstraaten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003316:Corneal Diseases / Q000175:diagnosis* / Q000235:genetics; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D015995:Prevalence; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase
keywords: Cornea; Diagnostic tests/Investigation; Epidemiology; Genetics