Diagnosis of familial amyloid polyneuropathy: wide-ranged clinicopathological features

Abstract

Owing to the recent development of biochemical and molecular analyses, familial amyloid polyneuropathy (FAP) is not considered to be as rare as was previously thought. Transthyretin (TTR) Val30Met-associated FAP (FAP ATTR Val30Met) is the most common form of FAP. Although patients with FAP ATTR Val30Met had been considered to be concentrated in geographically restricted areas of Japan, Portugal and Sweden, a late-onset form of this type of FAP was discovered in non-endemic areas and revealed to be widely distributed throughout the world. Therefore, there is an increasing necessity to characterize the variability in the clinical, electrophysiological and histopathological features of this disease. Recent progress in the diagnostic techniques for FAP is described, focusing especially on those for FAP ATTR Val30Met. Clinical, electrophysiological and histopathological features in early-onset FAP ATTR Val30Met cases from endemic foci and those in late-onset cases from non-endemic areas in Japan are comparatively described. Patients with FAP ATTR Val30Met from endemic foci and those from non-endemic areas show different clinical, electrophysiological and histopathological features. As compared with the classic FAP phenotype, the clinicopathological features of patients from the non-endemic areas tend to be nonspecific. Awareness of the possibility of sporadic late-onset FAP ATTR Val30Met is needed at the time of the initial clinical and electrophysiological evaluation of neuropathy with an undetermined etiology to avoid a missed diagnosis.