Contributor: Gordon K. Klintworth
Amyloid deposition within the peripheral nerves is a prominent features of numerous inherited types of amyloid polyneuropathy: familial amyloid polyneuropathy type I, familial amyloid polyneuropathy type II, Familial amyloid polyneuropathy type IIA, familial amyloid polyneuropathy type III, familial amyloid polyneuropathy type IV, familial amyloid polyneuropathy type V, familial amyloid polyneuropathy type VI..
The amyloid protein in familial amyloid polyneuropathy type IV (Meretoja or Finnish type, lattice corneal dystrophy type II) is a type of systemic amyloidosis. The cornea is involved [lattice corneal dystrophy type II]. The amyloid has been identified as a 71-amino acid long fragment (7-12 kDa) of gelsolin with an asparagine at codon 187 instead of aspartic acid. The same mutation has been found in American and Finnish families.
Familial amyloid polyneuropathy type I (Andrade or Portuguese type, transthryretin methionine substitution for valine at position 30) was first documented by Andrade in 1952 in patients from a small region in northwestern Portugal. The disorder begins with a loss within the lower extremities of thermal, superficial pain, touch, and position sense in that order. Common manifestations include an early impotence in the male, perforating ulcers of the feet, diarrhea, sphincter disturbances, and weight loss. Amyloid deposition occurs throughout the body in blood vessels. Clinically significant renal disease is absent. The pupils become irregular in contour, unequal in size, and dilated with absent or sluggish reactions to light and accommodation. The pupil develops a characteristic scalloped appearance (this is also a feature of other types of familial amyloid polyneuropathy). Ocular signs and symptoms may result from the neuropathy, vascular fragility or vitreous opacification.
The amyloid fibrils lack both AA protein and AL protein, but a major component of them is a protein (molecular mass about 14 kDa) with antigenic determinants and an electrophoretic mobility similar with transthyretin. Amino acid sequence analysis of the purified amyloid has disclosed it to consist of part of a variant transthyretin in which methionine is substituted for valine in position 30. This mutation has been identified in persons of Portuguese, Japanese, Swedish, Greek and other origins.
Familial amyloid polyneuropathy type II (Rukavina, Indiana or Swiss type)(transthyretin-84 isoleucine to serine) is another type of tranthyretin amyloidosis that begins later in life and progresses more slowly than familial amyloid polyneuropathy type I [amyloid polyneuropathy type I]. The hands are affected and the carpal tunnel syndrome is a distinguishing feature. Ecchymoses of the eyelids, extraocular muscle weakness, internal ophthalmoplegia, and anisocoria may occur. Extensive deposits of amyloid have been found in blood vessels, ciliary nerves and extraocular muscles, but not in the iris sphincter muscle or cornea. The amyloid in this disoder is a variant of transthyretin with a serine substitution for isoleucine at position 84. Familial amyloid polyneuropathy type IIA (Mahloudji, Maryland type)(transthyretin-58 histidine to leucine) resembles familial amyloid polyneuropathy II clinically, but the mutation in the transthyretin gene encodes for a histidine substitution for leucine at position 58.