The severity and distribution of amyloid deposition in the late-onset familial amyloidotic polyneuropathy (FAP) — a clinicopathological analysis of three autopsy cases

Abstract

In our previous studies of 17 autopsy cases of FAP, we confirmed marked amyloid deposition in the peripheral nerve tissues, autonomic nervous system, choroid plexus, cardiovascular system, kidneys, anterior and posterior roots of the spinal cord, spinal ganglia, thyroid and gastrointestinal tract. Most of the cases had initially developed peripheral nervous distrubances, autonomic dysfuncUon, cardiac conduction disturbances, or orthostatic hypotension between the age of 16 and 43. In the present study, the severity of amyloid depostion in three autopsy cases of the late-onset FAP was investigated pathologically, histochemically, and compared with that in the ordinary type. As initial signs and symptoms, two of the three late-onset cases showed sensory disturbances in bilateral lower extremeties at age 56 and 73, respectively, while the other manifested cardiac failure at age 54. The duration of clinical course to death in the three cases was 6 to 7 years, shorter than in the ordinary FAP cases (10.1 years on average). Histochemical and immunohistochemical approaches were utilized to detect amyloid deposition in various organs and tissues obtained from the cases at autopsy. In all cases, amyloid deposits in the peripheral nerve tissues, autonomic nervous system, and posterior and anterior roots of the spinal cord were slight or nearly absent. In two of the three cases, amyloid involvement was marked in the kidneys and thyroid, but slight in the cardiovascular system. In the other case, ~unyloid deposition was prominent in the cardiac wall, causing marked cardiac hypertrophy (690g). In all three cases, the severity of amyloid deposition in the other organs and tissues was generally slight, compared to the ordinary FAP cases. These data provide evidence that the severity and distribution of amyloid deposition correlate with the clinical manifestations and duration of late-onset FAP, although the mechanisms causing the delay of amyloid deposition are unknown.