174 Chapter 5 In conclusion, we showed that plasma lysoGb3 values can further fine-tune clinical phenotyping. We confirmed that in patients with lysoGb3 levels below 2.3 nmol/L (with a reference range 0.3-0.5) renal function remains within the normal range (figure 2) and cardiac morphological and functional parameters show slow progression over time and become abnormal only late in life (from the 7th decade of life onwards, figure 4 and 5). These findings are consistent with earlier observations that the risk of cardiovascular complications in female patients with a non-classical disease type (in whom lysoGb3 levels are usually below 2.3 nmol/L) is low and if they do occur it is late in life [2]. The seven male (non-classical) FD patients with lysoGb3 levels below 2.3 in this study showed a similar benign disease course. In our opinion this group is unlikely to benefit from Fabry specific therapy and may not even require routine follow up before the sixth decade of life. Within the group of patients with a plasma lysoGb3 between 2.3 and 40 nmol/L (mostly male patients with non-classical FD and female patients with classical FD), measuring plasma lysoGb3 can help to give additional insight into the expected clinical course. In patients with relatively low lysoGb3 levels and no- or minor clinical FD manifestations, prolonging the interval between clinical evaluations seems justified and –in our opinion- the potential effect of treatment should be weighed against the burden of lifelong infusions in consultation with the patient. While in patients with higher lysoGb3 levels, more rigorous follow up is warranted and treatment may be started with less restraint. Further multicenter studies are needed to confirm these findings and identify other biomarkers to improve clinical risk stratification of FD patients. Based on the results from this study, we propose that measuring plasma lysoGb3 at time of diagnosis can be a useful tool to help diagnose and classify FD. Additionally, the early stabilization of lysoGb3 in plasma over time makes it a suitable marker to aid clinical decision making, more specifically to help determine the needed frequency of follow and the timing of treatment initiation in asymptomatic patients.
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