Marco Spada1, Ralf Baron2, Perry M Elliott3, Bruno Falissard4, Max J Hilz5, Lorenzo Monserrat6, Camilla Tøndel7, Anna Tylki-Szymańska8, Christoph Wanner9, Dominique P Germain10. 1. Department of Paediatrics, University of Torino, Torino, Italy. Electronic address: marco.spada@unito.it. 2. Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany. 3. Barts Heart Centre, University College London, London, United Kingdom. 4. INSERM U1018, University of Paris-Sud, University of Paris-Descartes, Paris, France. 5. Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany. 6. Health in Code, A Coruña, Spain. 7. Department of Paediatrics, Haukeland University Hospital, Department of Clinical Medicine, University of Bergen, Bergen, Norway. 8. Department of Paediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland. 9. Division of Nephrology, University Clinic, University of Würzburg, Würzburg, Germany. 10. French Referral Center for Fabry disease, Division of Medical Genetics and INSERM U1179, University of Versailles, Paris-Saclay University, Montigny, France.
Abstract
BACKGROUND: Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.
BACKGROUND:Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.
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