Analysis of the effect of specific therapy on exercise capacity in patients with anderson-fabry disease

Background and Aim Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, which encodes the enzyme α-galactosidase. The accumulation of globotriaosylceramide (Gb3) in various tissues and organs underlies the clinical manifestations of the disease, which range from muscular involvement to renal, peripheral nervous system, and cardiac complications. Due to its X-linked inheritance, disease manifestations are more severe in males, whereas females generally present milder forms, likely due to X-chromosome lyonization. FD patients exhibit a wide range of symptoms related to Gb3 accumulation in multiple organs and tissues, among which fatigue and asthenia are among the most frequently reported. In this study, we aimed to analyze the effect of specific FD therapy, either with oral chaperone treatment or enzyme replacement therapy, on exercise capacity in FD patients. Methods FD patients who had undergone at least one bicycle ergometer stress test at our clinic were included in the analysis. Results From February 2021 to September 2022, we enrolled 59 patients. Table 1 summarizes the main characteristics of the study population and the key ergometer stress test parameters. Patients receiving ERT showed lower lactate concentrations at peak exercise (with a trend toward statistical significance compared to untreated patients), which translated into a statistically significant difference in lactate levels from baseline to peak exercise. No significant differences were found in demographic characteristics or other stress test parameters. Patients on specific FD treatment had been receiving therapy for 57 ± 53 months. For a subgroup of 15 patients (33% female) who had started specific FD therapy since our first evaluation we were able to evaluate the effects of this treatment in relation to the cardiopulmonary exercise test, as shown in Table 2. As shown in Table 2, in the subgroup of patients who had initiated specific therapy, after a mean follow-up period of 14 ± 5 months, we observed an increase in exercise duration of approximately 90 seconds (from 399 ± 123 seconds at baseline to 539 ± 239 seconds at the final follow-up; p = 0.034), along with an increase in METs from 8.7 ± 2.7 at baseline to 11.7 ± 5.2 at follow-up (p = 0.034). Conclusions The initiation of specific FD treatment in patients with Fabry Disease is associated with an improvement in exercise capacity, reflected by increased exercise duration and METs. Moreover, patients undergoing long-term specific FC treatment exhibited reduced metabolic acidosis, as assessed by lactate production during exercise, compared to those not receiving therapy.