what are the 3 types of amyloidosis

3 min read 13-03-2025

Amyloidosis is a rare disease characterized by the abnormal buildup of amyloid proteins in various organs and tissues. These amyloid deposits disrupt normal organ function, leading to a range of symptoms depending on the affected organs. While there are many subtypes, amyloidosis is broadly classified into three main types based on the source and type of amyloid protein involved: AL, AA, and ATTR amyloidosis. Understanding these distinctions is crucial for proper diagnosis and treatment.

1. AL Amyloidosis (Immunoglobulin Light Chain Amyloidosis)

Microscopic image of AL amyloid deposits

AL amyloidosis is the most common type. It stems from a problem within the bone marrow's plasma cells. These cells produce abnormal immunoglobulin light chains, which are fragments of antibodies. These misfolded proteins clump together, forming amyloid fibrils. The deposits can affect virtually any organ, including the heart, kidneys, liver, nerves, and digestive tract.

Causes and Symptoms of AL Amyloidosis

AL amyloidosis develops when the bone marrow produces too many abnormal light chains. The exact cause of this aberrant production is often unclear, but certain conditions like multiple myeloma increase the risk. Symptoms are highly variable and depend on the organs involved. They can include fatigue, shortness of breath, swelling in the legs and ankles, and unexplained weight loss. Kidney damage can lead to proteinuria (protein in the urine) and fluid retention. Heart involvement can cause heart failure.

Diagnosis and Treatment of AL Amyloidosis

Diagnosis involves a combination of blood tests, urine tests, and biopsies to identify the presence of amyloid deposits and determine their type. Treatment typically focuses on chemotherapy to suppress the production of abnormal light chains, as well as supportive care to manage organ damage. Stem cell transplantation may be an option in some cases.

2. AA Amyloidosis (Secondary Amyloidosis)

Illustration showing the formation of AA amyloid fibrils

AA amyloidosis is triggered by long-term chronic inflammation. In this type, amyloid fibrils are composed of serum amyloid A (SAA) protein. SAA is an acute-phase reactant protein produced by the liver in response to inflammation. Prolonged inflammation leads to excessive SAA production, which can then misfold and deposit as amyloid.

Causes and Symptoms of AA Amyloidosis

Conditions such as rheumatoid arthritis, inflammatory bowel disease, and infections can lead to chronic inflammation and, consequently, AA amyloidosis. The symptoms closely mirror those of AL amyloidosis and depend heavily on the organs affected. These can include fatigue, weight loss, and organ-specific symptoms like kidney failure or liver enlargement.

Diagnosis and Treatment of AA Amyloidosis

Diagnosis involves identifying the underlying inflammatory condition and confirming the presence of AA amyloid deposits through biopsies. Treatment centers on managing the underlying inflammatory disease. In some cases, medications like colchicine may be used to reduce amyloid formation.

3. ATTR Amyloidosis (Transthyretin Amyloidosis)

Molecular structure of transthyretin protein

ATTR amyloidosis involves the misfolding of transthyretin (TTR), a protein produced primarily by the liver. This protein normally transports vitamin A and thyroxine (a thyroid hormone) in the blood. However, genetic mutations or age-related changes can cause TTR to misfold and form amyloid deposits.

Causes and Symptoms of ATTR Amyloidosis

ATTR amyloidosis can be hereditary (caused by genetic mutations) or acquired (due to age-related changes). Hereditary ATTR amyloidosis often manifests at a younger age, while acquired ATTR typically appears later in life. Symptoms vary widely but often involve nerve damage (peripheral neuropathy), heart problems (cardiomyopathy), and digestive issues.

Diagnosis and Treatment of ATTR Amyloidosis

Diagnosis requires identifying the presence of amyloid deposits and determining whether it's TTR amyloid. Genetic testing may be necessary to confirm the hereditary form. Treatment options include medications that stabilize TTR and prevent further amyloid formation, liver transplantation (for hereditary forms), and supportive care to manage symptoms.

Conclusion

The three main types of amyloidosis – AL, AA, and ATTR – each have distinct underlying causes and may present with varying symptoms depending on the affected organs. Early diagnosis and appropriate treatment are critical for managing this complex disease and improving patient outcomes. If you suspect you may have amyloidosis, consult with a medical professional for proper evaluation and diagnosis. Further research continues to advance our understanding and treatment options for all types of amyloidosis.