The systemic amyloidosis types are all very different from each other with respect to the biochemical nature of the amyloid deposit. Some are acquired and others are inherited. Some types share clinical features of the disease. It is very important to define the amyloid type immediately when the diagnosis is made as treatments are different.
Primary Amyloidosis (AL)
Primary amyloidosis is an acquired plasma cell disorder in which a monoclonal immunoglobulin light chain is produced in the bone marrow and usually found in the blood or urine. AL amyloidosis occasionally occurs with multiple myeloma. The amyloid fibrils in this type of amyloidosis are made up of immunoglobulin light chain proteins (kappa or lambda).The short term for this type of amyloidosis is AL, for amyloid of light chain composition. Symptoms can occur in any organ of the body and include heart failure, protein in the urine or kidney failure, enlarged liver, neuropathy or enlarged tongue. Treatment with chemotherapy has been standard; however newer agents are in clinical trials and being found effective. This is the most common type of amyloidosis in the United States.
Secondary Amyloidosis (AA)
Secondary amyloidosis is caused by a chronic infection or an inflammatory disease such as rheumatoid arthritis, familial Mediterranean fever, osteomyelitis, or granulomatous ileitis. Infection or inflammation causes elevation of an acute phase protein, SAA, a portion of which (AA protein) deposits as amyloid fibrils. Thus, it is termed AA amyloidosis. AA amyloidosis usually begins as disease in the kidneys, but other organs can be affected. Medical or surgical treatment of the underlying chronic infection or inflammatory disease can slow down or stop the progression of this type of amyloid. A second clinical trial to evaluate a new treatment with a targeted inhibitor molecule, Kiacta, has just begun.
Familial Amyloidosis (ATTR)
There are several types of inherited amyloidoses, the most common of which is caused by a mutation in the transthyretin (TTR) gene that produces abnormal transthyretin protein. The abnormal TTR protein deposits as amyloid fibrils: thus, it is termed ATTR amyloidosis. Symptoms of disease are usually neuropathy and cardiomyopathy and occur in mid to late life. ATTR is found in families of nearly every ethnic background. More than 100 different mutations in transthyretin are known and most cause amyloidosis. Treatment is a liver transplant; however newer treatments with targeted inhibitors are in clinical trials.
Other familial amyloidoses
There are other gene mutations that produce proteins that cause amyloidosis. These are very rare. They include apolipoprotein A-I (AApoAI), apolipoprotein A-II (AApoAII) gelsolin (AGel), fibrinogen (AFib), and lysozyme (ALys).
Beta-2 Microglobulin Amyloidosis (Abeta2m)
Beta-2 microglobulin amyloidosis is caused by chronic renal failure and often occurs in patients who are on dialysis for many years. Amyloid deposits are made of the beta-2 microglobulin protein that accumulated in tissues, particularly around joints, when it cannot be excreted by the kidney because of renal failure.
Localized Amyloidosis (ALoc)
There are many types of localized amyloidoses. The most common and best known is Alzheimer’s disease. Localized amyloid deposits in the airway (trachea or bronchus), eye, or urinary bladder are made up of light chain proteins, similar to those in AL amyloidosis. However, in localized amyloidosis the abnormal plasma cells producing the amyloid light chains are in the tissues, not in the bone marrow. Other localized types of amyloidosis are associated with hormone proteins, aging, or specific areas of the body, and have not been found to develop into systemic amyloidosis.