Clinical and pathological findings of non-Val30Met TTR type familial amyloid polyneuropathy in Japan

Non-Val30Met TTR type FAP is being increasingly recognized; a total of 21 TTR gene mutations related to the development of non-Val30Met type FAP have been identified among Japanese. The clinical phenotypes of these FAP kindreds varied considerably corresponding to the different mutations of TTR gene. In the nervous system.. peripheral nerve involvement sometimes started as a carpal tunnel syndrome in addition to peripheral somatic and autonomic neuropathy. Brain and spinal cord dysfunctions due to leptomeningeal amyloidosis infrequently appeared. Severe involvement of the heart was a common finding in the visceral organs, which might causally lead to a poor prognosis for the patients with this form of FAR Several patients with ATTR non-Val30Met have recently undergone living-related partial liver transplantation, and their postoperative courses have been under careful investigation. organs'. This disease used to be considered to be peculiar to endemic areas, which representatively include Oporto in Portugal(2), the northern part of Sweden(3), and Arao(4) and Ogawa(1,5) in Japan. However, understanding of FAP has progressed greatly during the last twenty years; the variant form of transthyretin (TTR) is a main constituent of amyloid deposits in this disease(6), and more than 80 variants of TTR have been identified as possible amyloid precursors(7). In the vast majority of patients who showed the typical clinical picture of type I FAP, the disease was shown to be caused by ATTR Val30Met (the most common mutation of the TTR gene with the substitution of methionine for valine at position 30). The remaining FAP patients with ATTR non-Val30Met seem to have markedly different clinical phenotypes and also diverse pathological conditions corresponding to the varied TTR gene mutations. In this article, we present and summarize the current clinicopathological features of non-Val30Met TTR type FAP in Japan.