Abnormal transthyretin in asymptomatic relatives in familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) has been biochemically and genetically proven to be an inherited molecular disorder of transthyretin. (The term transthyretin has been suggested by the Nomenclature Committee of the international Union of Biochemistry and the International Union of Pure and Applied Chemistry for the protein that has heretofore been called prealbumin.) We have experienced three cases that included typical clinical, electrophysiologic, and neuropathologic manifestations of FAP, and yet no known family history of the disorder. The patients and members of their families were studied by radioimmunoassay for a variant transthyretin with a methionine-for-valine substitution at position 30. All three patients had the variant transthyretin in the serum, at concentrations of 54.5, 87.9, and 105.9 mg/L (5.45, 8.79, and 10.59 mg/dL). Although parents and siblings had neither neurologic nor electromyographic evidence of FAP, some of these family members had serum concentrations of variant transthyretin as high as those of the propositi. It was from these asymptomatic parents that the "nonfamilial" patients inherited the gene for FAP. Further study is needed to define the mechanisms retarding or preventing, as well as those promoting, the clinical development of FAP when the variant transthyretin is present in the serum at a high level.