Inherited amyloidosis.

The amyloidoses are a group of deposition diseases in which the tissue deposits are composed of protein fibrils. These fibrils are the result of aggregation of specific precursor proteins into ordered structures which are resistant to proteolytic digestion and solubilisation. The ordered structure of the fibrils causes the deposits to be birefringent and, when histological sections are stained with Congo red, a characteristic green birefringence is seen by polarisation microscopy. The amyloidoses can be classified into broad groups on the basis of distribution: (1) localised and (2) systemic (table 1). Both of these broad groups include hereditary and non-hereditary forms of deposition disease. Immunoglobulin (primary) amyloidosis is the most common form of non-hereditary systemic amyloidosis. In this disease the amyloid fibrils are composed of monoclonal immunoglobulin light chain molecules or degradation products of these light chains. Reactive (secondary) amyloidosis is usually seen in association with chronic inflammatory diseases. The amyloid fibrils in this disease contain a degradation product of the acute phase serum protein SAA. Amyloidosis associated with chronic haemodialysis has fibres synthesised from P2-microglobulin. While this type of amyloidosis is usually restricted to bones and joints, some systemic deposits may occur. The localised forms of non-hereditary amyloidosis include isolated amyloidosis of the genitourinary tract, isolated bronchopulmonary amyloidosis, lichen amyloidosis, most cases of Alzheimer's disease, the hyalinised islets of Langerhans in non-insulin dependent diabetes mellitus, and a number of others. Familial amyloidotic polyneuropathy (FAP) associated with variants of plasma transthyretin (prealbumin) represents the most frequent form of inherited amyloidosis. ' In these syndromes the amyloid fibril deposits contain the variant transTable I Systemic amyloidoses.