Learning About Amyloidosis

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Amyloidosis is a disease characterized by proteins abnormally depositing in various organs in the body. The hallmark of amyloidosis is the specific pattern of deposition – where the proteins deposit as tiny fibrils in a sheet-like fashion.

In amyloidosis, the specific type of protein that is deposited defines what kind of amyloidosis is present, and how serious the disease is. Because the underlying cause of amyloidosis is entirely different depending on which protein is being deposited, the treatment options are entirely different as well.

How proteins form into amyloid deposits

In many cases (such as "primary" or "familial" amyloidosis), amyloid deposits occur because the protein present in the body is abnormal. In such cases, the abnormal structure of the protein makes it more susceptible to forming into fibrils and depositing in tissues.

In other cases (such as "senile" amyloidosis), a normal protein is deposited – either because it is present in abnormally high quantities, or because it is present for many years. Other substances in the body are also present in amyloid deposits, and their contributions to forming amyloid deposits are being investigated.

Amyloid
Using a high-powered electron microscopy, each individual amyloid fibril can be seen.

Amyloidosis symptoms

Symptoms of amyloidosis vary greatly, depending on which organs in the body are affected.

Symptoms of amyloidosis may include:

Amyloidosis diagnosis

Amyloidosis is widely considered to be a rare disease. However, there is no doubt that it is vastly under diagnosed, and that many people die from complications of the disease without ever receiving a diagnosis. Indeed, the only way to diagnose amyloidosis is to think about the diagnosis.

Your doctor may be suspicious of a diagnosis of amyloidosis based on your clinical history and/or lab work, but the ultimate diagnosis requires demonstration of amyloid deposits on a biopsy. The site of the biopsy varies on where the amyloid deposits are suspected – common sites include abdominal fat, the bone marrow, the kidneys, or the heart. Biopsies are almost all outpatient procedures, meaning you do not need to be hospitalized overnight for them.

Types of amyloidosis

There are literally dozens of types of amyloidosis that have been identified – ranging in seriousness from trivial to life-threatening. Each kind of amyloidosis is given a name starting with "A" (which stands for "amyloid"), and ending with an abbreviation for the kind of protein deposited. For the purposes of brevity, we will focus on the most common types that cause important clinical manifestations:

Amyloid
Using this advanced imaging called "electron microscopy", amyloid deposits (labeled A) can be seen to infiltrate normal heart cells (labeled "H").

AL (primary) amyloidosis

This represents the most commonly diagnosed form of amyloidosis. In this disease, the body's immune system produces abnormal forms of antibodies (called "light chains" – the "L" in "AL" Amyloidosis). The light chains deposit as amyloid fibrils, and can affect many organs in the body –commonly including the heart, kidneys, nerves, and gut.

The most common cause of death is from heart failure and/or abnormal heart rhythms, which arise from amyloid infiltration of the heart. AL amyloidosis overall has the worst prognosis of the different forms of amyloid, but life expectancy varies significantly depending on each individual's specific case – and most importantly on the degree of cardiac involvement. Treatment of AL amyloidosis requires a twofold approach – optimizing the function of the involved organs (such as the heart), and decreasing the production of the abnormal light chains.

Familial ATTR amyloidosis

In this inherited disease, the body makes a mutant form of a protein called "transthyretin." (Transthyretin – also known as "prealbumin" – is abbreviated "TTR" and is the reason this disease is called "ATTR amyloidosis.") While everyone produces transthyretin, the mutated form is much more likely to form into amyloid fibrils. Many different mutations have been identified; one of the most common is called "Ile-122" and is particularly common in African-Americans.

This form of amyloidosis most commonly affects the heart and nerves; other organ involvement may occur, but is uncommon. Though it is a very serious disease, the prognosis for familial ATTR amyloidosis is overall better than AL amyloidosis, as it usually progresses at a slower rate. Because the liver produces the mutated transthyretin protein, the disease can be occasionally treated with a liver transplant if it is caught early enough. Multiple investigational medications are also being studied for this condition. Family genetic screening, which is available through the Stanford Amyloid Center, may be helpful if a family member has also been diagnosed with this disease.

Senile ATTR amyloidosis

This disease is similar to familial ATTR amyloidosis, but the protein that is deposited is the normal (non-mutated) transthyretin protein. Because the normal transthyretin protein is much less prone to forming amyloid deposits than the mutated form, patients only develop the disease in old age – most commonly at 80 years of age or older. Largely due to the fact that amyloid deposits accumulate slowly in this disease, the prognosis is much better than AL (primary) amyloidosis, and is often better than familial ATTR amyloidosis.

The most common site of clinically important amyloid deposits is the heart. Treatment involves supportive care (e.g. optimizing the function of involved organs such as the heart.)

Amyloid Kidney
Special staining reveals the amyloid deposits in the kidney in this patient are from AA (also known as secondary) amyloidosis. AA amyloidosis occurs as a result of chronic infections or chronic inflammatory disorders.

AA (secondary) amyloidosis

The protein in this disease is called "serum amyloid A" (accounting for the name "AA amyloidosis"). This protein is produced by the body in response to inflammation or infection. High levels of the protein do not cause amyloid deposits over the short term, but prolonged high levels can lead to amyloid deposits. For this reason, diseases which lead to chronic states of inflammation (e.g. poorly controlled rheumatoid arthritis) or to chronic states of infection (e.g. chronic tuberculosis) can result in AA amyloidosis deposits over several years.

Commonly affected organs include the kidneys, the liver, and the spleen; involvement of the heart is extremely rare. Treatment is aimed at the underlying cause of the inflammation or infection (e.g. controlling rheumatoid arthritis with immune suppressants or treating tuberculosis with appropriate antibiotics).

Treatment for amyloidosis

Because amyloidosis diagnoses are relatively uncommon, most clinicians have little experience taking care of patients with the disease. Many patients therefore prefer to receive care (or a second-opinion) at an amyloid center (such as Stanford), where patients with the disease are commonly cared for, and a treatment team experienced with the disease is present.

While there is no cure for amyloidosis, treatment therapies can effectively manage amyloid signs and symptoms.

Specific treatment options vary based on the type of amyloidosis. These include:

Be sure to speak with your doctor on what treatment option is best for you.

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