Familial amyloidotic polyneuropathy type 1 in Kumamoto, Japan: a clinicopathologic, histochemical,...

Seventeen autopsy and five biopsy cases of familial amyloidotic polyneuropathy were examined clinicopathologically, histochemically, immunohistochemically, and ultrastructurally. In the autopsy cases, amyloid deposits were predominant in the peripheral nerve tissues, autonomic nervous system, choroid plexus, cardiovascular system, and kidneys. Amyloid involvements in the anterior and posterior roots of the spinal cord, spinal ganglia, thyroid, and gastrointestinal tract were also frequent. In the cardiac conduction system, amyloid deposition was prominent in the sinoatrial node and in limbs of the intraventricular bundle. In the sural nerve biopsy, besides amyloid deposits, degenerative changes of nerve fibers and Schwann cells were detected ultrastructurally, and the morphometric analysis showed a marked reduction in the number of myelinated fibers which correlated with the clinical stage. Amyloid deposits were resistant to pretreatment with potassium permanganate in Congo red staining, and transthyretin was confirmed immunohistochemically as a major component of amyloid deposits, along with the presence of serum amyloid P-component. Besides the amyloid deposits, transthyretin was proven in the liver cells, epithelial cells of the choroid plexus, and pancreatic islet A cells, suggesting that the transthyretin produced by these cells is secreted, transferred into tissues, and deposited in situ as the major component of amyloid in this disorder.