Neurological manifestations of Fabry disease

The neurological manifestations of Fabry disease include both peripheral nervous system and CNS involvement, with globotriaosylceramide accumulation found in Schwann cells and dorsal root ganglia together with deposits in CNS neurones. The main involvement of the CNS is attributable to cerebrovasculopathy, with an increased incidence of stroke. The abnormal neuronal accumulation of glycosphingolipid appears to have little clinical effect on the natural history of Fabry disease, with the possible exception of some reported mild cognitive abnormalities. The pathogenesis of Fabry vasculopathy remains poorly understood, but probably relates, in part, to abnormal functional control of the vessels, secondary to endothelial dysfunction as a consequence of α-galactosidase A deficiency. Obstructive vasculopathy, either primarily due to accumulation of glycolipid or secondary to consequent inflammation and confounding vascular risk factors, may develop in response to abnormal endothelial and vessel wall function, similar in some respects to that observed with accumulation of cholesterol-laden lipids during atherosclerosis. Involvement of the peripheral nervous system affects mainly small Aδ and C fibres, and is probably causally related to the altered autonomic function and neuropathic pain found in Fabry disease. Other related neurological problems include hypohidrosis and other abnormalities associated with nervous system dysfunction.