Fabry Disease and Central Nervous System Involvement: From Big to Small, from Brain to Synapse

Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) secondary to mutations in the GLA gene that causes dysfunctional activity of lysosomal hydrolase alpha-galactosidase A and results in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). The endothelial accumulation of these substrates results in injury to multiple organs, mainly the kidney, heart, brain and peripheral nervous system. The literature on FD and central nervous system involvement is scarce when focusing on alterations beyond cerebrovascular disease and is nearly absent in regard to synaptic dysfunction. In spite of that, reports have provided evidence for the CNS' clinical implications in FD, including Parkinson's disease, neuropsychiatric disorders and executive dysfunction. We aim to review these topics based on the current available scientific literature.

Automated summary

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to dysfunctional lysosomal activity and the accumulation of specific substances in various organs. While research on central nervous system involvement in Fabry disease is limited, evidence suggests its clinical implications in conditions such as Parkinson's disease and neuropsychiatric disorders. This review aims to summarize the current scientific literature on these topics.