INTRODUCTION

Among the hereditary systemic amyloidosis, transthyretin (TTR) neuropathies (OMIM #176300) are devastating disorders with an autosomal dominant transmission, expressed mainly as a progressive fibre length dependent sensorimotor polyneuropathy and life threatening autonomic dysfunction.¹ Initially, the condition was recognised in northern Portugal, in the area of Povoa de Varzim, where the prevalence has been estimated at 1/1000.^2,3 Other important clusters of families were subsequently reported in Japan, initially in two limited geographic areas (the districts of Arao and Ogawa),⁴ and in the north of Sweden.⁵ The condition is now known throughout the world, including various European countries.⁶ Among the 75 pathogenic TTR variants identified so far, Val30Met is the most frequent, and is virtually the only one described in Portugal and Sweden.^7,8 By contrast, in Japan, the TTR point mutations are highly heterogeneous, with more than 20 different substitutions, including Val30Met, described.⁹ In France, a previous study found a similar heterogeneity.¹⁰ Depending on the geographic origin, the mean age of onset ranges from 30 to 70 years. A variable clinical expression is also observed, with restrictive cardiomyopathy, carpal tunnel syndrome, and vitreous opacities often encountered, whereas renal involvement is less common. These manifestations, along with the discrepancy in age of onset, account for phenotypic variations. However, virtually no genotype–phenotype correlation seems to exist. To supply the main source of mutant TTR, liver transplantation has been proposed as a treatment for the disease for the last 10 years, with promising results. In the Val30Met patients, it virtually suppresses the production of the mutant TTR in the serum and slows the progression of the neurological symptoms that otherwise have a fatal outcome in less than 10 years.¹¹ Another important aspect of the management of affected families is the recent availability of predictive …