title: Paediatric Fabry disease: prognostic significance of ocular changes for disease severity.
abstract: BACKGROUND
  Ocular signs of Fabry disease can be seen in the first decade of life.
  
  
  METHODS
  We examined the occurrence of ocular signs in 232 paediatric patients in the Fabry Outcome Survey (FOS) international registry and looked for relationships between the presence of eye findings and disease severity as measured by the FOS Mainz severity score index (FOS-MSSI).
  
  
  RESULTS
  At least one ocular sign was found in 55/101 (54.5%) girls and 62/131 (47.3%) boys: cornea verticillata in 53/101 (52.5%) girls and 55/131 (42.0%) boys, vessel tortuosity in 17/98 (17.3%) girls and 32/131 (24.4%) boys, and posterior spoke-like lens opacities in 3/97 (3.1%) girls and 2/130 (1.5%) boys. Summary statistics showed higher median (range) age-adjusted FOS-MSSI total score indicating more severe disease in children with eye findings versus those without eye findings (0.5 [-11.0, 20.7] versus -2.3 [-11.1, 18.8]). At least one eye finding was observed in 59.1% of treated and 37.9% of untreated children.
  
  
  CONCLUSIONS
  We conclude that the presence of ocular signs, particularly cornea verticillata, correlates with more severe disease as indicated by FOS-MSSI scores in paediatric patients with Fabry disease. Ocular signs appear in roughly half of school-aged children with Fabry disease and are well-recognised as a valuable tool for diagnosis of Fabry disease in children; they also may help identify patients who are at risk for developing early severe manifestations of Fabry disease and who should be further evaluated and closely followed up.
authors.affiliation: Department of Paediatrics, Helios-Dr-Horst-Schmidt-Kliniken HSK, Ludwig-Erhard-Strasse 100, 65199, Wiesbaden, Germany. g.kalkum@web.de.
authors.forename: Gisela
authors.initials: G
authors.lastname: Kalkum
authors.affiliation: Department of Ophthalmology, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Pitz
authors.affiliation: Department of Neuropaediatrics and Inborn Metabolic Disorders (Metabolicum Ruhr), University Children's Hospital, Centre for Rare Diseases, Ruhr University Bochum, Bochum, Germany.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Karabul
authors.affiliation: Institute of Human Genetics, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.affiliation: Department of Paediatrics, Germans Trias i Pujol University Hospital, and Research Institute IGTP, Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pintos-Morell
authors.affiliation: Rare Metabolic Diseases Unit, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.affiliation: Division of Metabolism, University Children's Hospital, Children's Research Centre, Zurich, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Rohrbach
authors.affiliation: Shire, Zug, Switzerland.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bizjajeva
authors.affiliation: Lysosomal Disorders Unit, Royal Free London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Uma
authors.initials: U
authors.lastname: Ramaswami
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002386:Cataract / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003315:Cornea / Q000002:abnormalities; D005124:Eye Abnormalities / Q000208:ethnology*; D005128:Eye Diseases / Q000209:etiology*; D000795:Fabry Disease / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012171:Retinal Vessels / Q000002:abnormalities; D012720:Severity of Illness Index; D012737:Sex Factors
keywords: Agalsidase alfa; Children; Fabry Outcome Survey; Fabry disease; Ocular signs