Fabry disease

This review discusses the literature on Fabry disease mainly in the domain of neurology with special attention to recent advancement.

Fabry neuropathy is known as a length-dependent peripheral neuropathy affecting mainly the small myelinated (Aδ) fibers and unmyelinated (C) fibers. Recently, concerning heterozygotes, it seems that they suffer from peripheral neuropathy at a higher rate than previously shown, significant multisystemic disease, and severely decreased quality of life. The existence of an atypical variant of Fabry disease with late-onset cerebrovascular disease (cerebrovascular variant) is now suggested, like the cardiac and renal variants of Fabry disease. Although enzyme replacement therapy (ERT) has been shown to have some positive effects on reduction of neuropathic pain, the improvement of detection threshold for thermal sensation and sweat function, the effect of ERT on the central nervous system has not been established. Gene replacement therapy, chemical chaperone therapy, and ERT using modified α-N-acetylgalactosaminidase are in progress, and induced pluripotent stem cells were generated from mouse models of Fabry disease.

Heterozygotes should be carefully monitored for precise estimation and adequate therapy. Early initiation of ERT before irreversible organ failure is most important, and alternative therapeutic approaches are currently being explored.