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

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5246
• Main Authors: Cortés-Saladelafont, Elisenda, Fernández-Martín, Julián, Ortolano, Saida
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Accumulation; alpha-Galactosidase - genetics; alpha-Galactosidase - metabolism; Brain - metabolism; Central nervous system; Cerebrovascular disease; Cerebrovascular diseases; Dementia; Fabry disease; Fabry Disease - genetics; Fabry's disease; Galactosidase; Genes; Genetic aspects; Genotype & phenotype; Globotriaosylceramide; Glycolipids; Humans; Kidney - metabolism; lysosome; Mental disorders; metabolism; Mutation; Nervous system; Nervous system diseases; Neurodegeneration; neurotransmission; neurotransmitter; Pain; Parkinson's disease; Pathogenesis; Pathology; Peripheral nervous system; Review; Sphingolipids; synapse; Synapses - metabolism; Germany; Spain; Fabry disease; metabolism; neurotransmission; synapse; neurotransmitter; lysosome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065246

Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) secondary to mutations in the gene that causes dysfunctional activity of lysosomal hydrolase α-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.