This is a disorder of protein metabolism in which there is extracellular deposition of insoluble fibrillar protein, either localized or widely distributed throughout the body.
Characteristically the amyloid protein consists of f3- pleated sheets that are responsible for the insolubility and resistance to proteolysis. A smaller part of the protein is the amyloid P component (AP), which is derived from normal circulatory glycoprotein and is related to the acute-phase reactant, C-reactive protein (CRP). Amyloid in tissues appears as an amorphous, homogeneous substance that stains pink with haematoxylin and eosin and stains red with Congo red, which also shows a green fluorescence in polarized light.
Hereditary systemic amyloidosis
In the Portuguese type I neuropathic amyloidosis, fibrils composed of prealbumin formed into f3 sheets are found, producing a polyneuropathy. In familial Mediterranean fever, renal amyloidosis is a common serious complication. Deposition of amyloid A (AA) fibrils occurs.
Deposits of amyloid fibrils of various types can be localized to various organs or tissues, e.g. skin, heart and brain. An amyloid syndrome due to f32-microglobulin deposition as amyloid fibrils is seen in patients on chronic dialysis.
Amyloid deposits are frequently found in the elderly. In particular, cerebral deposits of the A4 protein are found, and this protein is also seen in the brains of patients with Down’s syndrome and Alzheimer’s disease. Apoprotein E (involved in LDL transport, interacts directly with f3-A4 protein in senile plaques and neurofibrillary tangles in the brain. The gene for apoprotein E is on chromosome 19 and may be an important susceptibility factor in the aetiology of Alzheimer’s disease.
In this variety, the deposits consist of amyloid light (AL) chain fragments. The molecular weights of these fragments range from 5000 to 25000. The amyloidosis is usually associated with lymphoproliferative diseases of the Bcell lineage, e.g. myeloma, Waldenstrom’s macroglobulinaemia or non-Hodgkin’s lymphoma.
The clinical features are related to the organs involved, patients presenting with heart failure, nephrotic syndrome, purpura or bleeding, peripheral neuropathy or weight loss. Weakness and paraesthesia of the hand may occur due to the carpal tunnel syndrome. On examination, a characteristic feature is macroglossia, which only occurs in this form of amyloidosis. Hepatomegaly and occasionally splenomegaly are seen.
The diagnosis is made on the presence of the characteristic histological features mentioned above in a biopsy of the rectum or gums. The bone marrow may show plasma cells in primary amyloidosis or a lymphoproliferative disorder. A paraproteinaemia and light chains in the urine may be seen as a result of associated conditions.
Treatment is symptomatic or of the associated cause. Reactive systemic amyloidosis In reactive systemic amyloidosis, the amyloid (AA) is composed of protein A (molecular weight 8500), which is a precursor of the normal serum component serum amyloid A (SAA), an acute-phase reactant. Overproduction of SAA as well as its degradation to AA determines whether amyloidosis occurs. This type of amyloidosis, which used to be known as secondary amyloidosis, involves the spleen, liver, kidney and adrenal glands. It is associated with long-standing chronic infections (e.g. tuberculosis), inflammation (e.g. rheumatoid arthritis), malignancy (e.g. Hodgkin’s disease), and also occurs in familial Mediterranean fever.
Clinically there is hepatosplenomegaly. Hepatic failure and renal failure with renal-vein thrombosis or the nephrotic syndrome may develop,