Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy

Transthyretin amyloid neuropathy of type 1 (Swedish-Portuguese type) is an autosomally inherited progressive disease with a Val30Met mutation, causing generalized sensory-motor polyneuropathy. Quantitative sensory testing (QST) quantifies thermal threshold changes in patients with manifest general polyneuropathy, but its applicability at an early clinical stage of a strict biochemically defined disease has not yet been shown. Thermal QST was performed in 23 patients having a positive Val30Met marker and clinical symptoms of peripheral small-fiber neuropathy but normal electrophysiological findings and compared to a reference group of 43 healthy volunteers, both subdivided into age groups <= 45 and > 45 years. Significant differences between patients and controls were found at all test sites in both age groups, except for warm thresholds at the medial lower leg in those > 45 years. QST thus demonstrated elevated thermal thresholds before the development of electrophysiological abnormalities, which indicate large-fiber involvement, These findings confirm that QST is a useful method for documentation of developing polyneuropathy.