Recenti avanzamenti nella patofisiologia e diagnostica nella malattia di Fabry

AimFabry disease (FD) is a rare lysosomal storage disorder caused by deficiency of galactosidaseA that leads to cellular accumulation of glycosphingolipids, causing diffuse vascular damage. Recent scientific reports, including those of our group, led to a better knowledge both of pathophysiology and of biochemical diagnostic tools useful for early diagnosis of FD. We studied possible changes in motor cortex excitability in FD patients, using transcranial magnetic stimulation (TMS). Moreover, we evaluated if urinary glycosaminoglycan excretion could represent a marker for monitoring progressive kidney impairment in FD.MethodsWe measured the electrical threshold in the motor cortical representation of the right first dorsal interosseous, in 11 FD patients and 11 controls, through TMS protocols. In the biochemical study, quali-quantitative and structural analyses of plasma/urine from 24 FD patients and 43 control subjects were conducted.ResultsFD patients showed a significant increase of steepness in TMS protocols, which is indicative for an electrophysiological imbalance involving the glutamatergic excitatory circuits. Levels of urine bikunin resulted significantly higher in patients with renal involvement and were higher since early occurrence of renal impairment.ConclusionsFD have to be diagnosed in early stage of his course, before occurrence of irreversible structural and vascular damage in many vital organs. New diagnostic tools useful for early diagnosis are needed.