Epidemiology of familial amyloid polyneuropathy in Japan: Identification of a novel endemic focus

Background: Familial amyloid polyneuropathy (FAP) is distributed worldwide with several endemic foci including two major foci in Japan. Objective: To elucidate a nationwide epidemiology of FAP in Japan. Design, setting, and patients: (i) We analyzed the data of FAP patients registered by the Ministry of Health, Labour, and Welfare, Japan, during 2003-2005. (ii) As Ishikawa prefecture was found to be a novel endemic focus, we examined 27 FAP patients in Ishikawa to characterize their clinical and genetic features in comparison with other endemic foci. Results: (i) The prevalence of familial amyloidosis in Japan was estimated to be 0.87-1.1 per 1,000,000 persons. Nagano prefecture had the highest prevalence. (11-15.5), followed by Kumamoto (10.1-10.3), and then Ishikawa (3.5-4.2). (ii) All the FAP patients in Ishikawa had transthyretin (TTR) type FAP; all the families had a TTR Val30Met mutation except one family with a Leu58Arg mutation. FAP with Val30Met mutation in Ishikawa was characterized by late onset, high penetrance, and moderate autonomic dysfunction. Conclusions: Ishikawa prefecture is the third endemic focus of FAP in Japan. FAP with TTR Val30Met mutation in Japan can be classified to (i) early-onset and endemic (Nagano and Kumamoto), (ii) late-onset and endemic (Ishikawa), and (iii) late-onset and non-endemic types. (c) 2008 Elsevier B.V. All rights reserved.