Screening for Fabry disease and hereditary ATTR amyloidosis in idiopathic small fiber and mixed neuropathy

Abstract

Fabry disease (FD) and hereditary ATTR (hATTR) amyloidosis are treatable diseases known to cause small fiber neuropathy (SFN). The aim of this study was to explore the value of genetic screening for these 2 diseases. This was a retrospective and prospective multicenter study involving 9 participating neurology departments from 4 Nordic countries (Denmark, Finland, Norway and Sweden). Altogether, 172 patients were enrolled in this study. Of them, 17 were later excluded. Genetic sequencing of the GLA and TTR genes was performed. A single patient, 69-year old Swedish male, had a possible pathogenic variant, R118C, in the GLA gene, but the clinical investigations showed no definite signs of FD. No pathogenic mutations in the TTR gene were found, either. Our findings show that the yield of screening for FD and hATTR amyloidosis in patients with idiopathic SFN or mixed neuropathy without any clinical characteristics or disease-specific symptoms in a Nordic population appears to be extremely low in a clinical setting.