CNS manifestations of Fabryʹs disease

Summary Background Fabryʹs disease is a rare hereditary lysosomal storage disease with multiorgan involvement. Deficiency of α-galactosidase A activity leads to accumulation of neutral glycosphingolipids, especially in vascular endothelial and smooth-muscle cells. Along with progressive renal and cardiac dysfunction, stroke is a major and often life-threatening burden of the disease. Cerebral vasculopathy, confirmed by neuropathological, neuroradiological, and functional studies, occurs commonly and leads to ischaemic cerebrovascular events at an early age. Recent developments Fabryʹs disease is an X-linked disease and women have been regarded as only mildly affected carriers. However, research has shown a high prevalence of ischaemic stroke and transient ischaemic attacks, along with imaging evidence of CNS involvement, in female patients with the disease, which suggests that at least in a subgroup of clinically affected women the severity of CNS disease is comparable to that in men. Another study has shown a high prevalence of the disease in young patients of both sexes with cryptogenic stroke, emphasising the need for more clinical attention to be paid to this under-diagnosed disease. Where next? These new findings should be replicated in larger samples. Brain structural changes and CNS involvement in the disease need to be monitored carefully in follow-up studies to broaden our knowledge of the course of neurobiological changes and to identify potential effects of enzyme-replacement therapy, which is already showing some benefit in cardiac and renal dysfunction in the disease. Finally, a diagnosis of Fabryʹs disease should always be considered in young patients who have had a stroke.