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5 Types of Amyloidosis: AL, AA, Hereditary, and More

Medically reviewed by Richard LoCicero, M.D.
Written by Maureen McNulty
Updated on August 29, 2024

Amyloidosis is a group of rare diseases where abnormal proteins build up in the body. It’s grouped into different types based on the kind of protein involved. Each type may come with different symptoms, prognoses (outlooks), and treatment options. If your doctor diagnoses you with amyloidosis, they will also try to determine which type you have.

When normal cells make proteins, they fold the proteins in a very specific way. Sometimes, proteins become misfolded and clump together, building up inside different organs. The clumped proteins are called “amyloid fibrils” or “amyloid protein deposits.” Different types of proteins can build up in various places in the body, and in distinct quantities, leading to different types of amyloidosis. Most people only have one form of amyloidosis. However, it’s rare but possible for someone to have more than one type of amyloidosis at the same time.

Systemic vs. Localized Amyloidosis

Most types of amyloidosis are systemic. This means amyloid deposits occur throughout the body and are found in many kinds of tissue in different locations. The main types of systemic amyloidosis are:

  • Amyloid light-chain (AL) amyloidosis
  • AA amyloidosis
  • Hereditary amyloidosis
  • Wild-type ATTR (ATTRwt) amyloidosis

When amyloidosis is localized, this means amyloid proteins are only found in one specific area. Localized amyloidosis may occur in the bladder, airway, eye, or another organ. Localized amyloidosis may have a better prognosis (outlook) — although careful management is necessary, depending on the affected area of the body.

Dialysis-related amyloidosis is another form worth noting. It primarily affects people who’ve undergone long-term dialysis. Like systemic amyloidosis, this form involves widespread deposits, although these are often limited to the bones and joints. While not as common as the types listed above, it’s significant in individuals with severe kidney disease and warrants attention.

Following are details about these five types of amyloidosis.

1. AL Amyloidosis

Amyloid light-chain amyloidosis is also called “primary amyloidosis” or “primary systemic amyloidosis,” It’s the most common type of amyloidosis in the United States. About 4,500 people are diagnosed with AL amyloidosis in the U.S. each year. AL amyloidosis is more common in men and in people who are at least 50 years old.

This disease is caused by a condition or cancer of plasma cells — white blood cells that help fight infection. Plasma cells develop in the bone marrow. These cells make antibodies that recognize and fight off germs. Antibodies are proteins made up of multiple pieces, including immunoglobulin light chains and heavy chains. In AL amyloidosis, plasma cells make high levels of abnormal light-chain proteins. These light chains form amyloids — clusters of abnormal proteins that build up in different organs and cause problems.

AL amyloidosis has two subtypes. Two forms of light-chain proteins, known as kappa and lambda, can be responsible for amyloidosis. It may not be important to know which subtype of AL amyloidosis you have because both types are treated the same way and have similar outlooks.

Your prognosis with AL amyloidosis depends on how early the disease was diagnosed. For about 30 percent of people, this condition isn’t found until the organs are already seriously affected, and people in that situation may only live for a few months. If the disease is discovered earlier, the outlook is likely better. In particular, you may have a better prognosis if amyloidosis doesn’t affect your heart as severely. Your prognosis also depends on how well the treatment works. Your doctor can help you understand your outlook.

2. AA Amyloidosis

AA amyloidosis may also be called “secondary amyloidosis.” Unlike AL amyloidosis, the AA type develops as a response to another underlying disease that causes inflammation. Some illnesses that may lead to AA amyloidosis include:

  • Rheumatoid arthritis
  • Juvenile arthritis
  • Ankylosing spondylitis
  • Inflammatory bowel disease (IBD)
  • Certain ongoing infections
  • Hodgkin lymphoma
  • Renal cell carcinoma

When these diseases create inflammation, the liver makes a protein called serum amyloid A (SAA) protein. When too much of this protein is made over a long period of time, part of the SAA protein can form an amyloid deposit in tissues like the kidney, heart, and liver.

Having an inflammatory disease does not necessarily mean you’ll get AA amyloidosis. Fewer than 5 percent of people with these conditions develop amyloidosis. AA amyloidosis is the only type that can develop in children, although it more often affects adults.

One study of 374 people with AA amyloidosis found that the median survival period was approximately 11 years after diagnosis. Outcomes have improved in recent years, thanks to newer, more effective treatments. People with better kidney function are more likely to have good outcomes, although many people with this condition will have kidney failure and will require a kidney transplant.

3. Hereditary Amyloidosis

Hereditary or familial amyloidosis can be passed down from parent to child. Many different genes can cause this condition, and there are several subtypes of this disease. These subtypes fall under two main groups: ATTR amyloidosis or non-TTR amyloidosis.

Each subtype is caused by a specific gene mutation (variation). Normally, genes produce proteins that have different jobs within the cell. When a change occurs within a gene, it sometimes leads to proteins with certain abnormalities. In the case of hereditary amyloidosis, a gene mutation leads to a protein that forms an amyloid deposit. These gene mutations are something that you’re born with, but having the gene doesn’t necessarily mean you’ll develop amyloidosis.

Hereditary ATTR Amyloidosis

Hereditary ATTR (hATTR) amyloidosis is caused by a mutation in a gene that makes the transthyretin (TTR) protein. About 136 different gene changes can cause hATTR amyloidosis, so this disease often looks a little different from one person to the next. However, people within the same family will often have similar symptoms.

Your doctor may want to know exactly which TTR genetic mutation you have because individual mutations may be likely to affect different organs and require different treatments. This can be done with a sequencing test that “reads” the TTR gene from a blood sample. The most common mutation is called V30M.

People with hereditary ATTR amyloidosis typically live for an average of five to 15 years after symptoms begin. However, many factors may affect your outlook, including how early your symptoms started, which gene mutation you have, and which of your organs are affected by amyloid deposits. For this and other types of systemic amyloidosis, people are more likely to have a worse outcome if multiple organs are affected.

Non-TTR Amyloidosis

Many other gene mutations can also lead to amyloidosis, although these subtypes are all much more rare. Some of the other gene mutations that cause hereditary amyloidosis include:

  • Fibrinogen A alpha chain
  • Apolipoprotein A1
  • Apolipoprotein A2
  • Gelsolin
  • LECT2
  • Cystatin C

Each of these genes may also have multiple mutations. For example, scientists currently know of 22 different genetic changes in the apolipoprotein A1 that can cause amyloidosis. Clinicians need to figure out which specific genetic change you have before determining the optimal treatment program.

4. Wild-Type ATTR Amyloidosis

Wild-type ATTR amyloidosis is another type of amyloidosis caused by the TTR protein. Doctors used to call this disease “senile systemic amyloidosis” or “senile cardiac amyloidosis,” but these terms are not used anymore.

There are a few key differences between ATTRwt amyloidosis and hereditary ATTR amyloidosis. First, in ATTRwt amyloidosis, the TTR gene is normal and does not contain a mutation, but it still produces amyloid. Health experts do not yet understand how the normal TTR gene can cause amyloid deposits without any underlying gene mutations.

Second, while hereditary ATTR amyloidosis is passed down within families, ATTRwt amyloidosis is not. Instead, it is a disease of aging, most commonly diagnosed in men over age 70, according to Mayo Clinic.

ATTRwt amyloidosis usually causes heart problems. Because some older adults have heart issues caused by other diseases, doctors may not always realize when a person’s heart symptoms are caused by amyloidosis. This means some people may have this condition without realizing it.

People with ATTRwt amyloidosis often have a better outlook than individuals with other types of amyloidosis.

5. Dialysis-Related Amyloidosis

Dialysis-related amyloidosis — also called ABM2 amyloidosis — sometimes develops in people who’ve been on kidney dialysis for many years. When someone’s kidneys stop working properly, it becomes harder to filter toxins and wastes out of the body. People with kidney disease may need to undergo a procedure called dialysis, in which a machine filters the blood to remove extra waste. However, dialysis is not always effective at eliminating a protein called beta-2 microglobulin. This protein can prompt amyloid fibrils to build up in joints and tendons. People with dialysis-related amyloidosis often develop carpal tunnel syndrome and other joint problems.

Usually, only people with severe kidney disease can develop this type of amyloidosis. Dialysis has improved in recent years and is now less likely to cause this disease.

How Do You Know Which Type of Amyloidosis You Have?

In diagnosing amyloidosis, your doctor can determine which specific type you have. You may need to have blood or urine tests before being diagnosed. Additionally, your doctor may perform a biopsy, in which a sample of tissue is removed and studied under a microscope. This can help your doctor determine exactly which protein deposits are collecting in your organs. Your doctor may also use genetic tests to look for certain gene mutations that can cause amyloidosis.

Once your doctor determines the specific type of amyloidosis you have, they can tailor an amyloidosis treatment plan that’s best suited to your condition. This personalized approach helps target the underlying cause of amyloid deposits and manage symptoms more effectively, improving your overall prognosis and quality of life.

Join the Conversation

On MyAmyloidosisTeam, the social network for people with amyloidosis and their loved ones, more than 2,000 members come together to ask questions, give advice, and share their experiences with others who understand life with amyloidosis.

What type of amyloidosis do you have? What advice do you have for others living with that type? Share your experiences in the comments below, or start a new conversation on your Activities page.

References
  1. Protein Misfolding and Degenerative Diseases — Nature Education
  2. If You Have Multiple Myeloma — American Cancer Society
  3. What Is Amyloidosis? — Stanford Medicine Health Care
  4. Two Types of Amyloidosis Presenting in a Single Patient: A Case Series — Blood Cancer Journal
  5. Types of Amyloidosis — Boston University Chobanian & Avedisian School of Medicine: Amyloidosis Center
  6. Amyloidosis — Mayo Clinic
  7. AL Amyloidosis — Amyloidosis Foundation
  8. What Is New in Diagnosis and Management of Light Chain Amyloidosis? — Blood
  9. AA (Secondary) Amyloidosis — Stanford Health Care
  10. AA Amyloidosis — Amyloidosis Foundation
  11. Amyloidosis — National Organization for Rare Disorders
  12. Natural History and Outcome in Systemic AA Amyloidosis — The New England Journal of Medicine
  13. Presentation, Survival, and Prognostic Markers in AA Amyloidosis — QJM: An International Journal of Medicine
  14. Hereditary Amyloidosis — Amyloidosis Foundation
  15. The Amyloidoses: Clinical Features, Diagnosis and Treatment — Methodist DeBakey Cardiovascular Journal
  16. Hereditary Transthyretin Amyloidosis Overview — Neurological Sciences
  17. Familial Transthyretin Amyloidosis — Genetic and Rare Diseases Information Center
  18. Amyloidosis — Harvard Health Publishing
  19. Wild-Type ATTR Amyloidosis — Amyloidosis Foundation
  20. Wild-Type (Senile) ATTR Amyloidosis — Stanford Medicine Health Care
  21. Amyloidosis & Kidney Disease — National Institute of Diabetes and Digestive and Kidney Diseases
  22. What Is Amyloidosis and 10 Signs You Might Have It — Mayo Clinic News Network

Updated on August 29, 2024
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What Is The Life Expectancy Of An 84 Year Old Man, Diagnosed Two Years Ago With Wild ATTR? He Takes Vyndamax Regularly.

March 25, 2024 by A MyAmyloidosisTeam Member
Richard LoCicero, M.D. has a private practice specializing in hematology and medical oncology at the Longstreet Clinic Cancer Center, in Gainesville, Georgia. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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