Type I (transthyretin Met30) familial amyloid polyneuropathy in Japan - Early-vs late-onset form

Background: Type I (transthyretin Met30) familial amyloid polyneuropathy (FAP TTR Met30) occurs in 2 endemic foci in Japan. We have also reported late-onset-Japanese cases unrelated to an endemic focus and showing distinctive clinicopathologic features. Objective: To compare clinical and geographic features of FAP TTR Met30 between patients with onset before and after 50 years of age. Design and Setting: Clinical information was obtained through a nationwide survey by the Study Group for Hereditary Neuropathy in Japan. Results: Families with early-onset disease in this study numbered 82, and those with late onset, 59. In families with late onset, neuropathy showed male preponderance, low penetrance, little relationship to endemic foci, sensorimotor symptoms beginning distally in the lower extremities with disturbance of both superficial and deep sensation, and relatively mild autonomic symptoms. Families with early onset showed higher penetrance, concentration in endemic foci, predominant loss of superficial sensation, severe autonomic dysfunction, and atrioventricular nodal block requiring pacemaker implantation. Conclusions: This study confirmed differences in clinical and geographic features between early- and late-onset FAP TTR Met30. Late-onset cases may be more prevalent and widespread than previously believed.