Autosomal-dominant transthyretin (TTR)-related amyloidosis is not a frequent CMT2 neuropathy 'in disguise'

Abstract Transthyretin (TTR)-related familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant, systemic disease. First symptoms usually occur from the second to over sixth decade of life with a length-dependent axonal neuropathy with prominent involvement of the small fibers and multi-organ systemic failure. Early diagnosis is pivotal for effective therapeutic options, but it is hampered by the heterogeneity of the clinical spectrum which can lead to misdiagnosis with other neurological condition/disorder such as axonal sensory-motor neuropathy (CMT2) as described in literature. The aim of our study was to search for TTR mutations in a large cohort of selected undiagnosed axonal sensory-motor neuropathy patients to establish if misdiagnosis is frequent or rare in the Italian population. No TTR pathogenic variants were found in our cohort. In conclusion, our study shows that TTR testing not should be straightforward recommended in CMT2 patients but only when “red flags” TTR’s features are present.