Amyloidosis Facts

What is Amyloidosis?

Amyloidosis is a protein deposition disease in which proteins normally made in the body become abnormal and then misfold to form insoluble fibrils that deposit and damage tissues and organs. Many types of amyloidosis are described based on the nature of the misfolded protein. When amyloid forms, it can impact virtually any part of the body except the central nervous system (brain and spinal cord). Organs, including the heart, kidney, liver and intestine, as well as peripheral nerves, are most commonly involved. Light chain amyloidosis (AL), a common form of the disease is rare with an incidence of five to 12 persons/million/ year. AL is caused by defective plasma cells in the bone marrow, similar to multiple myeloma.  

Another common form of systemic amyloidosis occurs due to misfolding of transthyretin (TTR), a protein made in the liver. Abnormalities of TTR can occur as a result of a genetic mutation as seen with hereditary TTR amyloidosis (hATTR) or due to advanced age as seen with wild-type TTR amyloidosis (wtATTR). While there's currently no cure for amyloidosis, there are a variety of treatment options available. At City of Hope, we are committed to providing superb care for all patients with amyloidosis as well as research to improve our understanding of the disease and discovery of new treatments.

Types of Amyloidosis

Light Chain Amyloidosis (AL)

The misfolded protein that forms amyloid can come from various sources, but the most common is blood cells that live primarily in the bone marrow. All blood cells come from a precursor cell called a hematopoietic stem cell that lives in the bone marrow. One type of white blood cell is a plasma cell. 

A plasma cell's job is to make proteins that form antibodies (immunoglobulins). Among the proteins produced by plasma cells are light chains and heavy chains. A multitude of combinations of heavy and light chains occurs to make a variety of immunoglobulins. In AL, a small population of abnormal plasma cells makes too much protein of a single type (monoclonal gammopathy). The clonal, abnormal light chains misfold to form amyloid fibrils. Amyloid then deposits in tissues and organs, causing damage. AL can manifest as either systemic, affecting many organ systems, including the heart and kidneys, or localized impacting just one organ most typically the airways or bladder. The amyloid deposition can be either systemic-wide or localized to a single organ.

Transthyretin (TTR) Amyloidosis

TTR is a protein made in the liver responsible for carrying thyroid hormone and retinoic acid (vitamin A) throughout the circulation. The TTR protein generally circulates as a tetramer in four separate parts or subunits. When these subunits become disassociated, they can become unstable and misfold to form amyloid fibrils which then deposit into tissues and organs. TTR can occur due to a genetic mutation causing protein instability followed by misfolding of the protein to form amyloid. This form of systemic amyloidosis is known as hereditary amyloidosis and occurs more commonly in specific ethnic populations, including those of Portuguese or African American descent.

The other form of TTR occurs due to older age, and the normal TTR protein (wild type/senile) becomes amyloidogenic and then deposits in organs, primarily the heart.

Secondary Amyloidosis

Secondary amyloidosis is a unique disease unrelated to plasma cells or transthyretin. It develops from a precursor protein called amyloid precursor protein that, when exposed to chronic inflammation for a prolonged period, becomes amyloidogenic. The organs involved with secondary amyloidosis are primarily the kidneys and nervous system, but other organs can also become involved.

Other Amyloidosis

In addition to the three most common types, of amyloidosis, there are other more rare types including LECT2 and AP2M, and the Afib, Alys, ApoA1 and Agel. The multiple types of amyloidosis differ in their presentation as well as treatment requirements. Understanding the type of amyloid a patient has is paramount to guiding treatment and management. 

Risk Factors

The exact cause of amyloidosis is largely unknown, but several factors may contribute to a person's risk of developing the disease, including:

  • Age: People over age 50 are more likely to have amyloidosis.
  • Medical history: If you have a chronic inflammatory disease, your risk for amyloidosis may be increased.
  • Genetics: A family history of amyloidosis increases the risk of hereditary forms of the disease.  
  • A diagnosis of multiple myeloma also increases the risk of developing AL. Between 10% and 15% of people with multiple myeloma also have amyloidosis.

Signs and Symptoms of Amyloidosis

It can be challenging to recognize amyloidosis early, as the symptoms are often similar to those of other diseases. Because amyloidosis can affect various organs, symptoms present differently for each patient. Here are some signs that you may have amyloidosis:

  • Fatigue (most common)
  • Joint pain
  • Tingling or numbness in the hands, arms, legs and feet
  • Difficulty breathing and shortness of breath
  • Skin rashes
  • Diarrhea
  • Enlarged tongue
  • Organ dysfunction like nephrotic syndrome, restrictive cardiomyopathy or gastrointestinal dysmotility
  • Autonomic or sensory and motor neuropathy
  • Swollen eyes
  • Anemia
  • Hepatomegaly or increased alkaline phosphatase
  • Unintentional weight loss