Familial transthyretin-type amyloid polyneuropathy in Japan: clinical and genetic heterogeneity.

Familial amyloid polyneuropathy (FAP) was once considered a disease peculiar to endemic areas, but it is now recognized not to be a rare disease among hereditary neuropathic disorders in Japan. FAP in Japan, the majority of which is caused by transthyretin (TTR)-related amyloid deposition, shows a wide spectrum of clinical pictures. This variability can be explained on the basis of the many causative gene mutations of TTR, but even in the same TTR type of FAP, the clinical phenotypes seem to vary in different kindreds or individuals. Especially in the case of the Val30Met TTR type, the sex ratio and the age at onset are considerably different between patients in endemic foci and those in nonendemic areas. It is also noteworthy that serious cardiac amyloidosis is commonly seen in patients with FAP of the non-Val30Met TTR type. In addition to TTR gene mutation, unknown factors may play an important role in the development of FAP. At present, liver transplantation is the only life-saving treatment, but this therapy is always associated with great stress for the patient and the donor, particularly in living-related transplantation. Less invasive treatments for this disease are required.