What Is the Main Cause of Amyloidosis?

Amyloidosis results from a buildup of insoluble amyloid fibrils (abnormal proteins) in the body’s tissues.

Amyloidosis is a rare condition that occurs when there is a buildup of insoluble amyloid fibrils (abnormal proteins) in the body’s tissues. These amyloid proteins alter the normal function of organs and can result in life-threatening organ failure.

There are several types of amyloidosis:

• Light chain (AL) amyloidosis is the most common type in the U.S. and is caused by a bone marrow disorder. It often affects multiple organs but does not affect the brain.
• AA amyloidosis occurs as a reaction to another illness, usually severe and chronic inflammatory diseases or infections. AA amyloid deposits develop in all tissues, but the most commonly damaged organ is the kidneys.  
• Hereditary amyloidosis is caused by an inherited gene mutation that produces amyloid protein that forms into an abnormal shape. This form is usually not noticed until adulthood and many carriers of the mutation have no symptoms or only minor ones. 
• Wild-type ATTR amyloidosis (also called ATTRwt and senile amyloidosis) is related to aging, it most commonly affects the heart, and occurs more frequently in men. 
• ALECT2 amyloidosis occurs when a particular protein in the blood that is soluble becomes insoluble. It frequently affects the kidneys and liver. 
• AB2M amyloidosis (also called B2M amyloidosis, Abeta2m, and DRA, for dialysis-related amyloidosis) occurs with end stage kidney failure after a patient has been on dialysis for many years.

Amyloidosis can affect any part of the body and symptoms depend on the type of amyloidosis and the tissues and organs affected. Symptoms may include: 

• Chronic kidney disease that can result in nephrotic syndrome 
  • Large amounts of protein in the urine (proteinuria) which may result in foamy urine
  • Fluid retention (edema), especially in the legs
  • Renal failure
  • Low levels of protein (albumin) in the blood 
  • High cholesterol
• Heart failure and other heart problems
  • Shortness of breath
  • Irregular heartbeats (arrhythmia)
  • Congestive heart failure
  • Chest pain
  • Low blood pressure/lightheadedness
• Gastrointestinal tract
  • Nausea
  • Diarrhea
  • Constipation
  • Weight loss
  • Loss of appetite
  • Feeling of fullness after eating
  • Slow stomach emptying
• Nerves
  • Pain, numbness, and tingling in hands, feet, and lower legs
  • Loss of sensitivity to temperature 
  • Dizziness on standing 
  • Nausea
  • Diarrhea
• Other symptoms
  • Enlarged liver and spleen (hepatosplenomegaly)
  • Carpal tunnel syndrome 
  • Joint pain
  • Chronic fatigue
  • Weakness
  • Bruising around the eyes or other areas
  • Swollen/enlarged tongue
  • Enlarged shoulders (“shoulder pads”) causing a restriction in the joint due to swelling 
  • Enlarged thyroid

Amyloidosis results from a buildup of insoluble amyloid fibrils (abnormal proteins) in the body’s tissues. There are a number of different types of amyloidosis which have different causes, such as:

• AA amyloidosis is caused by a reaction to another illness, usually severe and chronic inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease, or infections such as tuberculosis
• Hereditary amyloidosis is caused by an inherited gene mutation 
• ALECT2 amyloidosis occurs when a particular protein in the blood that is soluble becomes insoluble
• AB2M amyloidosis (also called B2M amyloidosis, Abeta2m, and DRA, for dialysis-related amyloidosis) occurs with end stage kidney failure after a patient has been on dialysis for many years

The primary way amyloidosis is diagnosed is with a tissue biopsy. Tissue may be taken from affected organs such as the kidneys, liver, heart, nerves, and other organs to confirm amyloid deposits. 

Other tests to diagnose amyloidosis include:

• Blood tests for liver function and thyroid hormones
• Serum-free light chain test
• Urine tests for amyloid protein levels
• Echocardiogram (ECG) of the heart
• Bone marrow aspiration and biopsy 
• Subcutaneous fat aspiration
• Magnetic resonance imaging (MRI) of organs

If amyloidosis is diagnosed, tests are used to determine which type of amyloidosis is present:

• Immunostaining
• Protein electrophoresis

There is no cure for amyloidosis. The goal of treatment is to relieve symptoms and slow the progression of the disease. 

Medications used to treat amyloidosis include:

• Medicines to treat diarrhea, nausea, and vomiting
• Pain relievers
• Diuretics
• Blood thinners
• Antiarrhythmics 
• Tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) for heart muscle damage (cardiomyopathy)
• Patisiran (Onpattro) and Inotersen (Tegsedi) to treat nerve damage (polyneuropathy) caused by hereditary amyloidosis 
• Chemotherapy drugs such as melphalan, cyclophosphamide (Cytoxan), bendamustine (Treanda)
• Proteasome inhibitors such as bortezomib (Velcade), MLN9708 (Ixazomib), carfilzomib (Kyprolis), gantenerumab, tocilizumab
• Immunomodulators such as thalidomide (Thalidomid), lenalidomide (Revlimid), pomalidomide (Pomalyst)
• Doxycycline to reduce joint pain and increase range of motion
• Stem-cell transplantation 
• Dialysis
• Organ transplants
• Special diet, for example, low sodium

Because amyloidosis can affect any organ, there can be many complications. 

• If the kidneys are affected: 
  • Kidney (renal) failure
  • Dialysis
• If the heart is affected:
  • The heart rhythm may be disrupted
  • Congestive heart failure
• If the nervous system is affected:  
  • Pain, numbness, and tingling in hands, feet, and lower legs
  • Loss of sensitivity to temperature 
  • Dizziness on standing 
  • Diarrhea