Learning about Amyloidosis
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.
Why are there so many kinds of amyloidosis?
"Amyloidosis" is a generic term used any time proteins are deposited in the fibril/sheet-like fashion noted above. Which specific protein 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.
What makes the proteins form into amyloid deposits?
In many cases (such as "Primary" or "Familial" amyloidosis), it occurs 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 or B 2 microglobulin" 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. Ultimately, what we don't know about what causes amyloid deposits to form is much greater than what we do know.
Using a high powered electron microscopopy, each individual amyloid fibril can be seen.
I have been diagnosed with amyloidosis. What now?
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" – where patients with the disease are commonly cared for and a treatment team experienced with the disease is present.
How common is amyloidosis, and how is it diagnosed?
Amyloidosis is widely considered to be a rare disease. However, there is no doubt that it is vastly underdiagnosed, 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 labwork, 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.
What types of amyloidosis are there?
There are literally dozens of types of amyloidosis which 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 which cause important clinical manifestations:
- 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 (Familial) 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 amyloid most commonly affects the kidneys and nerves; heart involvement is less common, occurring in approximately 25% of patients. Though it is a very serious disease, the prognosis for Familial ATTR amyloidosis is overall better than AL amyloidosis, largely because heart involvement is less common. Because the liver produces the mutated transthyretin protein, the disease can be successfully treated with a liver transplant if it is caught early enough. Family genetic screening is also critical if a family member has been diagnosed with this disease, and is available through the Stanford University Amyloid Center.
- Senile ATTR (Senile) Amyloidosis: This disease is similar to Familial ATTR amyloidosis, but the protein which is deposited is the normal (nonmutated) 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.)
- 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).
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.
- Dialysis-related (AB2m) Amyloidosis: This form of amyloidosis occurs in patients due to the accumulation of a protein called B2 -microglobulin. Because this naturally-produced protein is normally cleared from the body by the kidneys, it can accumulate in patients with end-stage kidney disease. The predominant manifestations of B2m amyloidosis are abnormalities of the joints and bones; death from the disease is very rare. With newer dialysis techniques, the incidence of B2m amyloidosis is much less than it used to be.