The Fabry Exercise Intolerance Study

Fabry disease (FD) is an inherited, highly variable and slowly progressive X linked disorder, which predominantly affects vascular endothelium, the heart, kidneys and the brain. Exercise intolerance is a complaint expressed by the majority of patients, at all stages of the disease. The exact cause, extent and development over time of exercise intolerance in FD in insufficiently understood. This limits preventive measures and adequate treatment.


Many patients with FD report exercise intolerance. This is described by patients as (muscle) fatigue, lack of endurance capacity or breathlessness. These symptoms limit the patient’s ability to participate in work and daily activities, leading to reduced mobility and independence. Simultaneously, it is one of the features of FD that is most difficult to tackle, as the origin of exercise intolerance is often not clear, limiting the possibility for giving individualized medical advice. Lack of interventions result in persistence of the problem and more immobility, resulting in a vicious cycle. The relationship between complaints and cardiac dysfunction is not always clear. However, exercise intolerance symptoms may also result from changes in lung or skeletal muscle function, or may be the result of deconditioning. Furthermore, recent studies have clearly shown that lysosomal storage disorders such as FD cause mitochondrial dysfunction. Whether this also occurs in both cardiac and skeletal muscle in FD and contribute to exercise intolerance in FD will be determined in this study.

Objectives of the study

1. To study the presence and extent of exercise intolerance in male and female FD patients with classical FD, and men with non-classical FD, in different stages of the disease.

2. Determine the etiology of exercise intolerance in FD.


This is a monocenter cross-sectional cohort study, in a cohort of Fabry patients that is under follow up at the Amsterdam UMC (location AMC). Data on exercise intolerance are collected by performing intermittent and maximal incremental cardiopulmonary exercise testing, and muscle strength testing with an optional muscle biopsy to detect skeletal muscle alterations.

Inclusion criteria

This study will include adult men with a definite diagnosis of either classical or non-classical FD and women with a definite diagnosis of classical FD. In addition, healthy adult control subjects, matched for sex, age and BMI to the FD patients will be included.

Start date/expected completion

Start date: 10-2021

Expected completion: 10-2023


B.C.F. Veldman, PhD student
M. Langeveld, principal investigator
Department of Endocrinology and Metabolism, F5-169
Amsterdam UMC, location AMC
Meibergdreef 9
1105 AZ Amsterdam
T 0031-20-5666071 E