Lower lean tissue mass in male Fabry disease patients and the burden of disease: findings from dual X-ray absorptiometry body composition

Abstract Introduction Fabry disease (FD) is an X-linked sphingolipidosis characterized by pathogenic variants in the GLA gene, which affect alpha-galactosidase A activity. Studies on body composition in FD patients have shown conflicting results. There is significant variability in weight and body mass index (BMI) among FD patients, likely due to chronic inflammatory status, gastrointestinal and renal disturbances, inactivity, exercise intolerance, and medications. However, there is no study that evaluate body composition using dual-energy X-ray absorptiometry (DXA) in FD patients compared to healthy controls. Objectives To assess body composition by DXA in Brazilian male FD patients and to compare the findings with those of healthy controls (HC). Additionally, to correlate the DXA measurements with Lyso-Gb3 concentrations, the main substrate accumulated in the disease. Method Fifteen genotype-confirmed classic male FD patients and 20 sex/age-matched HC had body composition evaluated by DXA. Lyso-Gb3 levels were obtained for FD patients. Results Mean age was 44.2 ± 12.3 years and 44.9 ± 11.8 years in FD patients and HC, respectively ( p = 0.87). BMI in FD patients (22.9 ± 3.7 kg/m 2 ) was not statistically different from HC (24.8 ± 2.4 kg/m 2 , p = 0.07). Appendicular lean mass was lower in FD patients (20,324 ± 2808 g) than HC (25529 ± 2535 g, p < 0.0001), as well as the appendicular lean mass index (7.24 ± 0.89 vs. 8.72 ± 0.80 kg/m 2 , p < 0.0001). There were no differences between patients and controls regarding fat mass or fat percentage. Lyso-Gb3 levels were inversely correlated with lean mass ( r = - 0.63, p = 0.01), fat mass ( r = - 0,68, p = 0.005) and fat percentage ( r = - 0.64, p = 0.01). Conclusion Adult FD patients in this cohort had lower lean mass than controls. Lyso-Gb3 accumulation is associated with lower values of lean mass, fat mass and fat percentage in FD patients.