Fabry disease model: a rational approach to the management of Fabry disease

Fabry disease (FD) is a truly progressive, multisystemic disorder. Clinically, the disease will present with 2 different faces throughout the lifetime of a patient: peripheral neurologic involvement predominates the symptoms in the first 3 decades of life (early symptoms), whereas major clinical events in the kidneys and heart or cerebrovascular system (late complications) largely determine the morbidity and mortality after 30 years of age. Before clinical manifestations occur in any organ system, there appears to be an insidious, subclinical progression of disease activities in various organ systems. Different stages of disease progression are associated with varying prognoses and potential responses to therapy, which provide a strong rationale for early intervention. Different stages may also be associated with various secondary pathologic events, which can provide indications for the use of a combination of interventions meant to control the primary pathology (lysosomal storage) as well as modifiable pathologies or correctable failures. A rational approach to FD and the therapy options available may help determine treatment choices and define therapeutic objectives as a function of optimal health outcomes, adequately reflecting the actual stage of disease progression, in individual patients.