Transthyretin-related familial amyloidotic polyneuropathy-Progress in Kumamoto, Japan (1967-2010)-

Abstract

The authors reviewed contribution of Kumamoto University group to the progress of the studies on transthyretin (TTR)-related familial amyloidotic polyneuropathy (TTR-related FAP) for 42 years (from 1967 to 2009). Andrade (1952) first described a large group of patients with FAP in Portugal and Araki et al. (1967) in second discovered similar FAP patients in Arao, Kumamoto, Japan. Owing to progress in biochemical and molecular genetic analyses, FAP is now believed to occur worldwide. As of today, reports of about 100 different points of single or two mutations, or a deletion in the transthyretin (TTR) gene, have been published. The authors' group has made pioneer works for study of FAP in the world. The focus on therapy in amylodosis will increase sharply as an impetus in near future, and successful treatments are expected.

Figure 1.

Distribution of FAP in the world. Locations of foci of FAP ATTR Val30Met patients described in previous reports and obtained from personal communications are presented.

Figure 2.

Distribution of FAP in Japan. Localization of various types of FAP patients in previous reports are presented in this figure.

Figure 3.

FAP patients in each clinical stage. Typical features of FAP patients in each clinical stage as described in ref. are demonstrated in the pictures.

Figure 4.

Clinical manifestations in patients with FAP ATTR Val30Met. One hundred sixty-nine patients with FAP ATTR Val30Met were registered from 1968 to 2003 in Arao district, Kumamoto, Japan.

Figure 5.

Working hypothesis for TTR amyloid formation and therapies. On the basis of amyloid formation mechanism, several promising therapies are considering.