Last updated:
6/17/2026
Years published: 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1995, 1996, 1997, 1998, 1999, 2001, 2002, 2003, 2006, 2007, 2010, 2013, 2016, 2018, 2023, 2026
NORD gratefully acknowledges Vaishali Sanchorawala, MD, Director of Amyloidosis Center, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center and Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for their assistance in the preparation of this report.
Summary
Amyloidosis is a group of diseases that happen when certain proteins in the body fold the wrong way. These misfolded proteins clump together and form deposits called “amyloid.” Normally, proteins are broken down at about the same rate as they are made, but amyloid deposits are unusually stable, they build up faster than the body can clear them. Over time, amyloid collects in organs like the heart, kidneys, nerves, or liver and keeps them from working properly. Eventually, if untreated, the affected organ can fail.
Amyloidosis can affect the whole body (called systemic amyloidosis) or just one area (called localized amyloidosis). Localized amyloidosis most often shows up in the bladder or airway (trachea) and does not usually spread to other organs.
There are different kinds of amyloidosis, depending on which protein causes the problem. Each protein affects the body in its own way, so your symptoms and treatment plan may vary based on the type you have. Doctors name each type with an “A” for amyloid, followed by letters that stand for the specific protein involved. Below are the main types.
AL Amyloidosis (historically called “primary” amyloidosis): The most common form of systemic (whole-body) amyloidosis. It happens when certain white blood cells in the bone marrow called plasma cells develop an abnormality (called a plasma cell dyscrasia) and produce abnormal light chain proteins (part of an antibody). These abnormal light chain proteins, or sometimes the whole antibody molecule, build up in body tissues as amyloid deposits. AL amyloidosis is closely related to a blood disorder called multiple myeloma. In about 2% of cases, a type of lymphoma (B-cell lymphoma) is the underlying cause instead.
AA Amyloidosis (historically called “secondary” amyloidosis): Caused by a protein called serum amyloid A, which increases during inflammation. This type often appears in people who have long-term (chronic) inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, chronic juvenile arthritis, ankylosing spondylitis, inflammatory bowel disease, or familial Mediterranean fever. It can also develop in people with chronic infections such as tuberculosis, leprosy, bronchiectasis, chronic bone infections (osteomyelitis), or chronic kidney infections (pyelonephritis). About half of people with AA amyloidosis have rheumatoid arthritis as the underlying condition. AA amyloidosis occurs in fewer than 5% of people with these conditions.
Hereditary (Familial) Amyloidosis: A rare form that runs in families. It is caused by changes (mutations) in certain genes that lead to abnormal proteins forming amyloid deposits. The most common type of hereditary amyloidosis is called ATTR and is caused by changes in the transthyretin (TTR) gene. More than 150 different TTR gene changes have been reported, and the most common one is called V30M. Rarely, hereditary amyloidosis can be caused by changes in other genes, including fibrinogen A alpha chain, apolipoprotein A1 and A2, gelsolin, LECT2, and cystatin C. All forms of hereditary amyloidosis follow an autosomal dominant pattern of inheritance, meaning only one copy of the changed gene (inherited from either parent) is needed to potentially cause the disease. Each child of an affected parent has a 50% chance of inheriting the gene change. The risk is the same for boys and girls. However, not every person who inherits the gene will develop symptoms.
ATTR Amyloidosis: Caused by a anomalies in a protein called transthyretin (TTR). There are two forms:
ATTRv (variant/hereditary): Caused by a mutation in the TTR gene that runs in families. Different TTR gene variants can affect different organ systems.
ATTRwt (wild-type/age-related): Happens when normal (unmutated) transthyretin protein builds up in the heart over time. It is a slowly progressive disease that tends to affect older adults, especially men and less commonly women. ATTRwt is probably the most common form of amyloidosis overall, but it is considerably underdiagnosed.
Dialysis-Related Beta-2-Microglobulin Amyloidosis (AB2MG): This type can develop in people who have been on long-term kidney dialysis (a process that filters waste from the blood when the kidneys cannot). It also occurs in some people on continuous ambulatory peritoneal dialysis (CAPD) and in some people with near end-stage kidney failure. It happens when a protein called beta-2-microglobulin, which is normally removed by healthy kidneys, builds up in the body over time. Although this buildup is believed to be the main factor, additional factors are needed for the disease to develop, which is why only some people on dialysis get this form. People with a functioning kidney transplant, or with normal or only mildly reduced kidney function, generally do not develop this form.
Amyloidosis is usually a disease that affects multiple body systems, which means it can present with many different signs and symptoms. Because of this, a patient may first see or be referred to different specialists, most commonly a kidney doctor (nephrologist), heart doctor (cardiologist), or nerve specialist (neurologist). Most patients have more than one organ involved.
The signs and symptoms of amyloidosis are different for each person. They depend on the type of amyloidosis, which organ are affected and how these affected organs are impacted.
Even people with the same type may notice different symptoms. Some symptoms are general and can make amyloidosis harder to recognize at first:
Other symptoms are more specific and depend on which organs are involved. Finding a combination of the symptoms below should raise suspicion for amyloidosis:
Kidneys
The kidneys are the organ most commonly involved in AL and AA amyloidosis, but are rarely involved in hereditary (familial) amyloidosis. The usual sign of kidney involvement is too much protein leaking into the urine (proteinuria), which is often heavy enough to cause a condition called nephrotic syndrome. Nephrotic syndrome can cause swelling in the legs and abdomen (even without heart failure), and high cholesterol levels in the blood. Less commonly, the first sign of kidney disease is a buildup of waste products in the blood (called azotemia). The kidneys may become small, pale, and hard, but in amyloidosis they can also appear large.
Heart
The heart is commonly involved in AL and ATTRv amyloidosis and is the main feature of ATTRwt amyloidosis. It is rarely involved in AA amyloidosis. Amyloid deposits in the heart cause the heart walls to thicken and become stiff, making it harder for the heart to pump blood. In AL amyloidosis, heart failure can progress rapidly. Common symptoms of heart involvement include:
Nerves
Although less common than kidney or heart involvement, nerve problems (neuropathy) can be a significant issue in amyloidosis. Occasionally, it is the first and main feature of AL amyloidosis. In certain hereditary forms (especially V30M ATTR, originally known as familial amyloid polyneuropathy), nerve involvement is the primary feature. The neuropathy is often painful and may include:
In ATTRv amyloidosis, nerve problems are frequently accompanied by autonomic neuropathy (problems with the nerves that control automatic body functions), which can cause:
Important: Systemic amyloidosis does not involve the brain or spinal cord (central nervous system) and is not related to Alzheimer disease.
Liver and spleen
Some degree of liver involvement is common in AL amyloidosis and AA amyloidosis, but is not seen in ATTRv amyloidosis. In most patients, liver involvement does not cause symptoms at first. The most noticeable signs are an enlarged liver (hepatomegaly) and an enlarged spleen (splenomegaly). The liver may feel very hard, and blood tests may show elevated liver enzymes (especially alkaline phosphatase). Generally, the liver continues to function until late in the disease. A rise in bilirubin (a substance measured in blood tests) is a serious warning sign that may indicate liver failure. Liver amyloidosis rarely occurs alone and it is usually found along with amyloid in other organs. Amyloid in the spleen increases the risk of the spleen rupturing on its own (spontaneous rupture).
Digestive system (gastrointestinal tract)
Amyloid buildup in the digestive system can slow down the movement of food through the esophagus and intestines. This can cause:
Skin
Skin involvement is almost exclusively seen in AL amyloidosis and includes problems with soft tissue, skin, and blood vessels:
Some skin changes are so small they can only be seen under a microscope.
Lungs and respiratory system
Breathing problems in amyloidosis often go along with heart symptoms. In localized amyloidosis, amyloid deposits can block air passages in the nasal sinuses, voice box (larynx), throat (trachea), and airways (bronchial tree). Fluid collecting around the lungs (pleural effusion) is quite common in patients with heart failure from amyloidosis. Large, recurring pleural effusions that seem out of proportion to the degree of heart failure may suggest amyloid deposits in the lining around the lungs (pleural amyloidosis).
Joints and muscles
Joint problems (arthropathy) occur when amyloid builds up in the lining of joints (synovial membranes). This is seen in AL amyloidosis and occasionally in dialysis-related amyloidosis. The cartilage and joint fluid may also be affected. Symptoms are similar to rheumatoid arthritis. Amyloid deposits in muscle tissue can cause muscle weakness and changes that may look like a muscle disease (pseudomyopathy).
Bleeding problems
Amyloidosis can sometimes cause bleeding disorders. These may result from a shortage of certain clotting factors or from small amyloid deposits in blood vessels within the skin.
Dialysis-related (AB2MG) amyloidosis
This form usually affects the bones and joints. Initial symptoms include carpal tunnel syndrome, shoulder pain, and inflammation of the tendon sheaths of the hands. There have also been case reports of severe high blood pressure in the lungs (pulmonary hypertension) and heart failure.
Your care team can help you understand which symptoms to watch for based on your type of amyloidosis.
Amyloidosis is caused by proteins that fold abnormally and stick together to form fibrils (tiny fibers) in one or more body organs, systems, or soft tissues. These clumps of protein are called amyloid deposits, and they build up faster than the body can break them down. Over time, this causes the affected organ to work less and less well.
AL amyloidosis is usually caused by a plasma cell dyscrasia, an acquired (not inherited) abnormality of the plasma cells in the bone marrow. These abnormal plasma cells produce excess antibody protein, and the abnormal light chain portion (or sometimes the whole antibody) accumulates in body tissues as amyloid.
AA amyloidosis is caused by the inflammatory process that is part of the underlying disease. About 50% of people with AA amyloidosis have rheumatoid arthritis as the underlying condition.
Hereditary (familial) amyloidosis is caused by an abnormality in the gene for one of several proteins. The most common form is caused by a change in the transthyretin (TTR) gene. More than 150 different TTR gene changes have been reported, and the most common is called V30M. Different TTR gene changes are associated with amyloidosis that affects different organ systems. Rarely, changes in genes for other proteins, including fibrinogen A alpha chain, apolipoprotein A1 and A2, gelsolin, LECT2, and cystatin C can cause hereditary amyloidosis. All hereditary forms follow autosomal dominant inheritance: only one copy of the changed gene (from either parent) is needed to potentially cause the disease. Each pregnancy carries a 50% chance of passing the gene to a child, and the risk is the same for boys and girls. However, not every person who inherits the gene will develop amyloidosis.
Amyloidosis can affect people of all backgrounds, but some hereditary ATTR gene changes are seen more often in certain families or ethnic groups. Knowing this can help guide testing and care, but anyone can develop amyloidosis. Below are some of the most well-known hereditary ATTR variants.
The V30M variant affects people differently based on family background:
In Portugal and some Japanese areas: Symptoms often start early, in the 30s or 40s, with foot tingling or burning, digestive troubles, sweating changes, eye issues, nerve pain, and a strong family history.
In other Japanese regions, Sweden, and non-endemic areas: Symptoms begin later (around age 50–67), feel milder early on, affect the heart and muscles more, often lack a known family history, and affect men most.
T60A (Thr60Ala) – Irish communities: The T60A mutation causes hereditary ATTR amyloidosis and is common in people with roots in northwest Ireland (such as Donegal). A single changed gene in transthyretin makes sticky proteins that build up in nerves, heart, and gut, with symptoms starting in the 40s–60s (average onset around age 61). This variant causes both cardiomyopathy and polyneuropathy.
Early clues include carpal tunnel syndrome in both wrists, numbness or burning in the hands and feet, heart strain (shortness of breath, swelling), dizziness from low blood pressure.
Doctors can spot it through family history, blood and urine tests for proteins, heart ultrasound showing thick walls, nerve tests, or a simple genetic cheek swab confirming T60A. Catching it early lets treatments like tafamidis (TTR stabilizer) or gene silencer therapies slow things down.
Hereditary ATTR Variants
| Feature | V122I (Val122Ile) | V30M (Val30Met) | T60A (Thr60Ala) |
| Also known as | Val122Ile | Val30Met | Thr60Ala |
| Most commonly seen in | African American / West African ancestry | Portuguese, Japanese, Swedish ancestry | Irish and Irish-descended populations |
| Primary organs affected | Heart (cardiac amyloidosis) | Nerves, heart, gastrointestinal system | Heart, peripheral nerves |
| Typical age of onset | Usually after age 60 | 30s–40s (endemic areas) or later adulthood | Mid-life to later adulthood (50s–70s) |
| Common early symptoms | Shortness of breath, fatigue, leg swelling, carpal tunnel syndrome | Tingling or numbness in feet/hands, digestive problems, weight loss | Heart failure symptoms, carpal tunnel syndrome, mild neuropathy |
| Pattern of progression | Slowly progressive, primarily cardiac | Variable: can begin with nerve symptoms and later involve the heart | Often cardiac dominant with gradual nerve involvement |
| Family history | May or may not be known | Often strong family history | Common, though sometimes unrecognized |
| Who is affected more often | Men more than women | Men and women equally | Men more than women |
| Key notes | One of the most common hereditary ATTR variants in the U.S. | Most common cause of familial amyloid polyneuropathy worldwide | Frequently presents as heart disease before amyloidosis is recognized |
Dialysis-related beta-2-microglobulin amyloidosis is not fully understood. A normally functioning kidney clears beta-2-microglobulin from the body. In some people on long-term dialysis or continuous ambulatory peritoneal dialysis (CAPD), the kidneys cannot remove this protein, leading to its buildup. Some people with near-end-stage kidney failure have also developed this form. Although this buildup is believed to be the main factor, additional factors are needed, which is why only a percentage of people on dialysis develop this condition.
AL amyloidosis: It is estimated that about 4,000 new cases occur each year in the United States, though the actual number may be higher because of underdiagnosis or misdiagnosis. The disease affects men and women equally, but about 60% of patients referred to amyloid centers are male. AL amyloidosis has been reported in people as young as 20, but is typically diagnosed between ages 50 and 65.
AA amyloidosis: People at risk include those with chronic inflammatory diseases (such as rheumatoid arthritis, psoriatic arthritis, chronic juvenile arthritis, ankylosing spondylitis in children, inflammatory bowel disease, and familial Mediterranean fever) and those with chronic infections (such as tuberculosis, leprosy, bronchiectasis, chronic bone infections, and chronic kidney infections). AA amyloidosis occurs in fewer than 5% of people with these conditions.
Hereditary (familial) ATTR amyloidosis: This occurs in about 1 in 100,000 white Americans, and more commonly in African Americans (about 3.4% carry the gene change). It is also prevalent in Portugal, Sweden, Japan, Ireland, Spain, France, Finland, Germany, and Greece. Symptoms usually begin between ages 40 and 65.
ATTRwt amyloidosis: This is probably the most common form of amyloidosis overall, but it is considerably underdiagnosed.
Amyloidosis can sometimes be overlooked because its symptoms often look like those of more common conditions. When this happens, it may take longer to get the right diagnosis. Finding amyloidosis early is important, especially in AL amyloidosis, where early diagnosis is the key to survival and regaining quality of life, because early detection can help protect organs from further damage and allow treatment to begin sooner.
Recent advances in treatment have made early and precise diagnosis more important than ever. Doctors use several tests to figure out what type of amyloidosis a patient may have, including the following:
In difficult cases, specialized techniques are available:
Once amyloid is found on a biopsy, it is essential to determine the specific type and to evaluate which organs are affected. If the patient is an elderly man with heart involvement only, the most likely diagnosis is ATTRwt amyloidosis.
Treatment
The type of treatment depends on the type of amyloidosis and the person’s overall health. Given the complexity of the disease, it is recommended that treatment be done at a center with experience in amyloidosis, or at least having an initial evaluation at such a center, with ongoing communication during treatment with the local doctors.
AL amyloidosis
Treatment targets the abnormal plasma cells in the bone marrow, since they are the source of the problem. Chemotherapy is the cornerstone of treatment. Options include:
Medications active in multiple myeloma, such as bortezomib (Velcade) or lenalidomide (Revlimid), are also very effective in AL amyloidosis and have been shown to help patients whose disease has come back (relapsed). These drugs are often included in initial treatment as well.
The two most important factors that determine long-term survival with AL amyloidosis are: (1) the presence and extent of heart involvement, and (2) how well the blood disorder responds to treatment.
Supportive care is also very important. This includes treatment of congestive heart failure, attention to nutrition, and management of autonomic neuropathy and other symptoms.
ATTR amyloidosis (hereditary and age-related)
Several FDA-approved treatments are available:
Since the liver is the main source of TTR protein, liver transplantation may be performed in carefully selected patients whose disease is not too far advanced, to remove the source of the abnormal protein.
For ATTRwt amyloidosis, treatment has traditionally been supportive (managing symptoms), but the TTR stabilizers and vutrisiran described above are now approved for this condition as well.
Genetic counseling is recommended for anyone with hereditary amyloidosis and their family members.
AA amyloidosis
The main treatment is controlling the underlying inflammatory or infectious disease. Kidney transplant has been successfully performed for kidney damage caused by AA amyloidosis.
Dialysis-related (AB2MG) amyloidosis
In 2015, the FDA authorized the use of a medical device called the Lixelle Beta 2-microglobulin apheresis column to treat this form. The device works by removing the beta-2-microglobulin protein from the blood.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Internet Resources (from the provided text):
28. Amyloidosis Awareness: For patients and their support network. Amyloidosis Support Groups. March 2022. https://www.amyloidosissupport.com/AmyloidAwareBooklet.pdf
29. Basu A, Bogdan CA, Matute R. Dialysis-Related Beta-2m Amyloidosis. Medscape. Updated Sept 21, 2022. https://emedicine.medscape.com/article/246542-overview
30. What is Amyloidosis? Boston University Amyloid Treatment & Research Program. https://www.bu.edu/amyloid/about/what/
31. Amyloidosis. Mayo Foundation for Medical Education and Research. Aug 17, 2022. https://www.mayoclinic.com/health/amyloidosis/DS00431
New References Added (supporting information incorporated from clinical guidelines and recent studies):
32. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46-58. (ANDROMEDA trial — primary analysis) [1]
33. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-bortezomib-cyclophosphamide-dexamethasone in newly diagnosed amyloidosis: ANDROMEDA final survival analysis. Blood. 2026. (ANDROMEDA — final survival analysis confirming overall survival benefit) [2]
34. Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med. 2025;392(1):33-44. (HELIOS-B trial) [3]
35. Haring B, Hunt RP, Shadyab AH, et al. Cardiovascular disease and mortality in Black women carrying the amyloidogenic V122I transthyretin gene variant. JACC Heart Fail. 2023;11(9):1185-1196. [4]
36. Madhani A, Sabogal N, Massillon D, et al. Clinical penetrance of the transthyretin V122I variant in older Black patients with heart failure: the SCAN-MP study. J Am Heart Assoc. 2023;12(15):e028973. [5]
37. Selvaraj S, Claggett B, Shah SH, et al. Cardiovascular burden of the V142I transthyretin variant. JAMA. 2024;331(22):1929-1939. [6]
38. Ruberg FL, Maurer MS. Cardiac amyloidosis due to transthyretin protein: a review. JAMA. 2024;331(9):778-791. (V30M, T60A, and V122I variant epidemiology) [7]
39. Sanchorawala V. Systemic light chain amyloidosis. N Engl J Med. 2024;390(26):2484-2498. (AL amyloidosis treatment overview including SCT eligibility) [8]
40. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Systemic Light Chain Amyloidosis. Version 2.2026. (Mayo 2004 staging, treatment algorithms, SCT eligibility, neuropathy management, relapsed disease) [9]
41. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC Expert Consensus Decision Pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis. J Am Coll Cardiol. 2023;81(11):1076-1126. [10]
42. Kittleson MM, Ambardekar AV, et al. Transthyretin cardiac amyloidosis evaluation and management: 2025 ACC Concise Clinical Guidance. J Am Coll Cardiol. 2025. (Vutrisiran FDA approval for ATTR-CM, vitamin A supplementation guidance
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