Derralynn A Hughes1. 1. Lysosomal Storage Disorders Unit and Department of Haematology, Royal Free London NHS Foundation Trust and University College London, London, UK.
Abstract
PURPOSE OF REVIEW: This review explores the clinical and pathological features of Fabry disease. New modalities of imaging, biomarkers and long-term treatment effects are discussed. RECENT FINDINGS: Fabry disease is clinically heterogeneous, and in women the clinical severity has recently been linked to skewing of X-inactivation. Two phenotypes have been described, one with early onset manifestations is including pain and one with later onset single organ manifestations; however, the cardiac outcomes in these two groups appear similar. Fibrosis is found in renal and cardiac tissues on biopsy and appears to be a critical point in the pathology of Fabry disease after which response to enzyme replacement therapy is more limited. In-vitro studies have suggested that lyso-globotriaosylceramide may have an important role in the generation of fibrosis. Imaging, including cardiac magnetic resonance imaging, may have a role in detection of early stages of the disease. Long-term outcomes for patients treated with enzyme replacement therapy are now being described with some suggestion that patients treated at earlier points in the disease course may have better outcomes. SUMMARY: Recent advances in understanding pathology, disease processes and treatment effects may enable future rational targeting of treatment with improved outcomes.
PURPOSE OF REVIEW: This review explores the clinical and pathological features of Fabry disease. New modalities of imaging, biomarkers and long-term treatment effects are discussed. RECENT FINDINGS:Fabry disease is clinically heterogeneous, and in women the clinical severity has recently been linked to skewing of X-inactivation. Two phenotypes have been described, one with early onset manifestations is including pain and one with later onset single organ manifestations; however, the cardiac outcomes in these two groups appear similar. Fibrosis is found in renal and cardiac tissues on biopsy and appears to be a critical point in the pathology of Fabry disease after which response to enzyme replacement therapy is more limited. In-vitro studies have suggested that lyso-globotriaosylceramide may have an important role in the generation of fibrosis. Imaging, including cardiac magnetic resonance imaging, may have a role in detection of early stages of the disease. Long-term outcomes for patients treated with enzyme replacement therapy are now being described with some suggestion that patients treated at earlier points in the disease course may have better outcomes. SUMMARY: Recent advances in understanding pathology, disease processes and treatment effects may enable future rational targeting of treatment with improved outcomes.
Authors: Uma Ramaswami; Michael Beck; Derralynn Hughes; Christoph Kampmann; Jaco Botha; Guillem Pintos-Morell; Michael L West; Dau-Ming Niu; Kathy Nicholls; Roberto Giugliani Journal: Drug Des Devel Ther Date: 2019-10-25 Impact factor: 4.162
Authors: Maarten Arends; Marieke Biegstraaten; Derralynn A Hughes; Atul Mehta; Perry M Elliott; Daniel Oder; Oliver T Watkinson; Frédéric M Vaz; André B P van Kuilenburg; Christoph Wanner; Carla E M Hollak Journal: PLoS One Date: 2017-08-01 Impact factor: 3.240