Fabry disease is an X-linked lysosomal storage disorder that causes accumulation of glycosphingolipids in body tissues and fluids, leading to progressive organ damage and life-threatening complications. It can affect both males and females and can be classified into classic or later-onset phenotypes. The disease severity in females ranges from asymptomatic to the more severe, classic phenotype. Most females are hemizygous and the X-linked inheritance is associated with variable X-activation pattern and residual enzymatic activity. The heterogeneity of clinical presentation in females requires different approaches to diagnosis and management than males. A European group of 7 physicians, experienced in the management of Fabry disease, convened to discuss patient perspectives and published guidelines. The experts discussed the need to focus on psychological treatment in relation to individual coping styles when monitoring targets, and the lack of data supporting the use of plasma globotriaosylsphingosine over enzyme activity in the diagnosis of these patients. It was suggested that the high phenotypic variability in female patients may be related to the dynamic nature of the X-chromosome inactivation process and further understanding of this process could help predict the progression of Fabry disease in females and facilitate timely intervention. Due to the range of disease severity they exhibit, female patients with Fabry disease may require a more individualized treatment approach than males. Despite current recommendations, the experts agreed that early disease-specific treatment initiation in high-risk females could improve clinical outcome.

2nd Department of Internal Cardiovascular Medicine General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Nephrology and Endocrinology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Nephrology Hypertension and Rheumatology and Interdisciplinary Fabry Centre Münster University Hospital Münster Münster Germany

Department of Public Health University Federico 2 of Napoli Napoli Italy

Expert Center for Rare Genetic Cardiovascular Diseases Institute of Emergency for Cardiovascular Diseases Prof Dr C C Iliescu University of Medicine and Pharmacy Carol Davila Bucharest Romania

Inherited Kidney Diseases Nephrology Department Fundació Puigvert Institut Recerca Sant Pau Universitat Autònoma de Barcelona Barcelona Spain

Institute of Clinical Medicine Faculty of Health and Clinical Sciences Copenhagen University Copenhagen Denmark

Internal Medicine D Department of Nephrology Hypertension and Rheumatology and Interdisciplinary Fabry Centre Münster University Hospital Münster Albert Schweitzer Campus 1 48149 Münster Germany

Lysosomal Disorders Unit Addenbrooke's Hospital Cambridge UK

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