Pathology of familial amyloidotic polyneuropathy with TTR met 30 in Kumamoto, Japan

Seventeen autopsy and 12 sural nerve biopsy cases of familial amyloidotic polyneuropathy (FAP) with transthyretin (TTR) Met 30 were examined clinicopathologically. In the autopsy cases, amyloid deposits were prominent in the peripheral nerve tissues, autonomic nervous system, choroid plexus, cardiovascular system and kidneys. Amyloid involvement in the posterior and anterior roots of the spinal cord, spinal ganglia, thyroid and gastrointestinal tract were also frequent. In the sural nerve biopsy, degenerative changes corresponding in degree to the duration of the clinical course were observed in the endoneurium, and amyloid deposition occurred around the blood vessels. Electron microscopy revealed degenerative changes in the axon, myelin sheath and Schwann cells. The morphometric study showed decreased numbers of small-caliber myelinated fibers during the early stage. TTR was confirmed immunohistochemically as a major component of amyloid deposits. In transgenic mice carrying the human mutant TTR gene, amyloid deposition was observed in various organs except in the peripheral nerves and choroid plexus. Liver transplantation therapy to FAP patients has been carried out and future follow-up studies should investigate the effects of therapy.