157 Plasma globotriaosylsphingosine and the natural Fabry disease course Abstract Background Fabry disease is a very heterogeneous X-linked lysosomal storage disease. Renal, cardiac and cerebral disease manifestations differ greatly, even between patients of the same sex and with the same disease classification (classical or non-classical). A biomarker with a strong predictive value for the development of disease manifestations is needed to determine the need for Fabry-specific treatment and appropriate frequency of follow-up, since clinical manifestations of the disorder take decennia to develop. Methods We investigated the levels of plasma lysoGb3 levels over time and its association with disease - manifestations and -course in 237 untreated FD patients using linear mixed effect models. Results LysoGb3 levels are stable over time in plasma of untreated Fabry patients. Higher levels of lysoGb3 were associated with steeper decline in estimated glomerular filtration rate (eGFR, p=0.04) and a faster increase in albuminuria (measured as the urinary albumin to creatinine ratio, UACR, p<0.001), left ventricular mass (LVMi, measured on echocardiography, p<0.001), left atrial volume index (LAVI, p=0.003) and Fazekas score (p=0.003). Additionally, regardless of age, higher lysoGb3 levels were associated with higher relative wall thickness (RWT, p<0.001) and unfavorable functional markers on echocardiography, including septal mitral annular early diastolic velocity (e’, p<0.001) and the ratio of early trans mitral velocity (E) to e’ (E/e’, p=0.001). Conclusion LysoGb3 is a static, individual FD trait with a close relationship to clinical disease severity. Since it reaches stability well before clinical disease manifestations occur, measuring lysoGb3 at diagnosis provides insight into the expected natural disease course, facilitating clinical decision making. 5
RkJQdWJsaXNoZXIy MTk4NDMw