What Is Amyloidosis?
Amyloidosis is a rare medical condition characterized by the abnormal accumulation of amyloid proteins in various organs and tissues throughout the body. Amyloid proteins are normally produced in the bone marrow and are usually broken down and eliminated.
However, in amyloidosis, they are not broken down properly and instead accumulate in the organs, disrupting their normal function.
There are several types of amyloid proteins that can cause amyloidosis, and the specific type determines the organs affected and the severity of the condition.
What are the Types of Amyloidosis?
Amyloidosis can be classified into different types based on the specific protein that forms the amyloid deposits and the underlying cause of the condition.
- AL (Immunoglobulin Light Chain) Amyloidosis: It occurs when abnormal plasma cells in the bone marrow produce excessive amounts of immunoglobulin light chains, which are fragments of antibodies. These light chains then misfold and accumulate as amyloid deposits in various organs and tissues.
- AA (Amyloid A) Amyloidosis: AA amyloidosis, also called secondary amyloidosis, is caused by chronic inflammatory conditions, infections, or inflammatory arthritis. It is associated with the accumulation of a protein called serum amyloid A (SAA), which is an acute-phase reactant produced during inflammation. Chronic inflammation leads to the deposit of amyloid A protein in organs, particularly the kidneys and liver.
- ATTR (Transthyretin) Amyloidosis: Transthyretin (TTR) amyloidosis is caused by the accumulation of transthyretin protein. TTR is produced mainly in the liver and is involved in transporting thyroid hormone and retinol. Mutations in the TTR gene can lead to hereditary ATTR amyloidosis, while wild-type ATTR amyloidosis (also known as senile systemic amyloidosis) is typically a result of age-related changes in the protein. The condition affects various organs, including the nerves, heart, and gastrointestinal system.
- Aβ (Amyloid Beta) Amyloidosis: This type of amyloidosis is primarily associated with Alzheimer’s disease. In Alzheimer’s, amyloid beta protein accumulates in the brain and forms plaques, which are a hallmark feature of the disease. The exact mechanisms leading to the misfolding and aggregation of amyloid beta in Alzheimer’s disease are still under investigation.
- Dialysis-Related Amyloidosis (DRA): DRA occurs in some individuals who have undergone long-term dialysis for kidney failure. It is caused by the deposition of beta-2 microglobulin, a protein that is usually removed by the kidneys but can accumulate in the bloodstream when kidney function is impaired. The amyloid deposits often affect the joints, leading to pain and limited mobility.
- Hereditary Gelsolin Amyloidosis: This is a rare hereditary form of amyloidosis caused by mutations in the gelsolin gene. Gelsolin is a protein involved in cell structure and function. Mutations in this gene can lead to the accumulation of gelsolin amyloid in various tissues.
Signs & Symptoms of Amyloidosis
The symptoms of amyloidosis can vary depending on the organs affected and the extent of amyloid deposition. The disease is often progressive, and symptoms may develop slowly over time. Some of the common symptoms and signs of amyloidosis include:
- Fatigue: Feeling excessively tired or weak is a common early symptom of amyloidosis.
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- Weight loss: Unexplained weight loss may occur in some individuals with amyloidosis.
- Edema: Swelling, particularly in the ankles and legs, can be a result of fluid accumulation due to impaired organ function, especially in the kidneys and heart.
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- Shortness of breath: Amyloid deposits in the heart can lead to cardiomyopathy (weakened heart muscle) and result in breathlessness or difficulty breathing.
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- Irregular heartbeat: Amyloidosis affecting the heart may cause arrhythmias or palpitations.
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- Numbness and tingling: When the nervous system is affected, individuals may experience sensations of numbness, tingling, or pain in their extremities.
- Enlarged tongue: Amyloid deposits in the tongue can cause it to become enlarged and may result in difficulty swallowing or speaking.
- Skin changes: Waxy deposits of amyloid under the skin may cause noticeable skin changes, such as bruising easily or a rash-like appearance.
- Gastrointestinal problems: Amyloidosis can affect the digestive tract, leading to symptoms like diarrhea, constipation, or a feeling of fullness after eating.
- Kidney problems: Amyloid deposition in the kidneys can cause proteinuria (excess protein in the urine) and lead to kidney dysfunction.
- Liver enlargement: In some cases, amyloidosis may cause the liver to become enlarged.
It’s important to note that the symptoms of amyloidosis can be non-specific and overlap with those of other medical conditions, which can make diagnosis challenging. The disease may also progress without causing noticeable symptoms in some cases, leading to delayed detection.
Treatment for Amyloidosis
The treatment of amyloidosis depends on the specific type of amyloid protein involved, the organs affected, the extent of amyloid deposition, and the overall health of the individual. Since there are several types of amyloidosis, the treatment approach may vary significantly. Here are some general treatment strategies used for different types of amyloidosis:
AL amyloidosis treatment aims to reduce the production of abnormal immunoglobulin light chains. Treatment may involve chemotherapy or targeted therapy to target the plasma cells responsible for producing the abnormal proteins. High-dose chemotherapy followed by autologous stem cell transplantation may be considered for eligible patients.
The primary focus of AA amyloidosis treatment is to address the underlying inflammatory condition that is driving the production of amyloid A protein. Controlling the inflammation with medications (such as anti-inflammatory drugs or immunosuppressants) may help prevent further amyloid deposition.
Treatment for ATTR amyloidosis depends on whether it is hereditary or acquired (wild-type). For hereditary ATTR amyloidosis, the use of medications called TTR stabilizers or gene-silencing therapies can be considered to reduce the production of abnormal transthyretin. For wild-type ATTR amyloidosis, medications that stabilize transthyretin tetramers, such as tafamidis, have been used to slow disease progression.
Currently, there is no cure for Alzheimer’s disease or Aβ amyloidosis. Treatment primarily focuses on managing symptoms and improving the individual’s quality of life. Medications may be prescribed to manage cognitive symptoms, but they do not alter the course of the disease.
In DRA, the primary approach is to optimize dialysis treatment to reduce the levels of beta-2 microglobulin in the blood. Newer dialysis techniques and strategies have been developed to improve the clearance of this amyloidogenic protein.
