Elderly Asymptomatic Carriers and Late-Onset Cases of Familial Amyloidotic Polyneuropathy Detected by Radioimmunoassay

Abstract

Familial amyloidotic polyneuropathy (FAP) is an inherited amyloidosis related to structurally abnormal transthyretin. We have experienced five FAP patients who developed the disease in the sixth decade, and four cases who had typical clinical, electrophysiologic, and neuropathologic manifestations of FAP, and yet had no known family history of the disorder. The serum samples obtained from the cases and members of their families were studied by a radioimmunoassay for a variant transthyretin with a methionine-for-valine substitution at position 30. All cases had the variant transthyretin. Although parents and siblings of “non-familial” FAP cases had neither neurologic nor electromyographic evidence of FAP, some members had the variant transthyretin. The “non-familial” cases were inheriting the mutated transthyretin gene from the elderly asymptomatic parents. The serum level of the variant transthyretin of late-onset cases and elderly carriers was as high as that of FAP patients with the usual age of onset. Further study is needed to define the mechanisms which retard, prevent, or promote the clinical development of FAP when the variant transthyretin is present at a high serum level.