Amyloidosis comprises a variety of disorders characterized by abnormal deposits of protein fibrils in organs and other tissues. These fibrils are derived from normal proteins, but because of an inherited or acquired problem, they undergo changes causing them to build up in the body.
Signs and symptoms depend on the type of amyloidosis and which organs are involved. Diagnosing amyloidosis is often difficult, because many symptoms vary depending on the affected organ and can occur with other diseases. Depending on symptoms and the organs involved, a variety of tests may be needed for diagnosis.
Examples of tests include blood tests that evaluate hereditary amyloidosis, blood tests to determine abnormal production of proteins, organ specific biopsies (liver, fat, bone marrow, heart, lip), 24 hour urine analysis, cardiac echocardiograms, computed tomography (CT) scans, and scintigraphy with radioisotope labeled serum amyloid P component scanning (SAP).
Primary Amyloidosis (AL)
AL is the most common type of amyloidosis in the United States. It is an acquired disorder characterized by unregulated production of light chain protein by plasma cells within the blood and bone marrow. Light chain protein can be detected in the blood, urine and affected tissues including the skin, kidney, heart and digestive tract. AL is often associated with multiple myeloma. Primary amyloid is referred to as AL because of the amyloid of light chain composition.
AL often involves the heart, kidneys, gastrointestinal tract and nervous system. The most common symptoms are shortness of breath, fatigue, swelling of the ankles and legs, dizziness when standing, abdominal fullness especially after eating, diarrhea, weight loss, enlarged tongue, numbness of the arms and legs, and protein in the urine. AL can be treated with chemotherapy. Newer agents being investigated for treatment of other cancers (including myeloma) are effective against AL amyloidosis.
Secondary Amyloidosis (AA)
AA is caused by a chronic infection or inflammatory disease such as rheumatoid arthritis, familial Mediterranean fever, osteomyelitis or granulomatous ileitis. The infection or inflammatory process causes an increase of an acute phase protein, SAA, in which the AA portion deposits as amyloid fibrils. Secondary amyloid is referred to AA for this reason. This type of amyloid often starts in the kidneys, but may also affect other organs.
AA is often caused by a chronic infection or inflammation. The most common symptoms are attributed to the underlying chronic infection or inflammatory process. Amyloid protein deposits often occur primarily in the kidneys and can cause protein in the urine, swelling of the legs and feet and fatigue. Treatment AA is based on controlling the underlying disease process. Clinical trials may also be available.
Hereditary Amyloidosis (ATTR)
There are several types of ATTR. The most common is caused by a mutation in the transthyretin (TTR) gene, producing an abnormal transthyretin protein. Because the TTR protein deposits as amyloid fibrils, hereditary amyloidosis is often referred to as ATTR. This type of amyloid can occur in people of nearly all ethnic backgrounds and can be caused by any of more than 100 different genetic mutations. ATTR is most often inherited from a parent. If a person has a copy of the genetic mutation, each of his or her offspring will have a 50 percent risk of inheriting the abnormal gene. If a child does not inherit the gene, he/she cannot pass it to future generations.
ATTR affects the nervous system. Symptoms are numbness and tingling in the arms and legs, dizziness when standing and diarrhea. Family members can be affected differently despite having the same genetic mutation. ATTR has the potential to be cured with liver transplantation. ATTR can be effectively synthesized by the transplanted liver. Clinical trials are also available.
Hemodialysis-related or Beta-2 Microglobulin Amyloidosis (Abeta2m)
Abeta2m is caused by chronic kidney failure and often occurs in patients who have been on dialysis for many years. The amyloid deposits are made of beta-2 microglobulin protein that accumulate in tissues specifically around joints, because the proteins cannot be excreted by the kidneys.
Localized Amyloidosis (ALoc)
ALoc can cause a variety of diseases. The most common ALoc is Alzheimer’s disease. Other types are associated with hormone proteins, aging, or specific areas of the body. These disorders do not develop into systemic amyloidosis. Localized amyloid deposits in the airway, eye, or urinary bladder are made up of light chain proteins, similar to AL amyloidosis.