What is Amyloidosis?
Amyloidosis is the name given to a group of rare disorders in which certain proteins misfold (or change shape), and then clump together in bundles. These bundles are called amyloid, over time amyloid can build up in organs and tissues leading to progressive organ failure.
Over the past 20 years, major advances in diagnosis and treatment have greatly improved the lives of people suffering from these conditions.
Although amyloidosis is still considered incurable, the introduction of new treatments has resulted in many patients experiencing lasting remission and leading busy, productive lives.
Much research is being carried around the world to develop new treatments for all types of amyloidosis.
Early diagnosis remains essential for optimum treatment.
The rarity of these conditions, the lack of awareness and the fact that the symptoms mimic other more common diseases results in many patients being diagnosed late, often after seeing a number of doctors.
Read Crystal’s story about her father’s late diagnosis
Amyloidosis can be:
Acquired (develops over time and is not inherited)
or
Hereditary (caused by a gene change passed through families).
Most types of amyloidosis are described as systemic diseases, meaning the amyloid forming protein circulates in the blood and deposits in one or several organs of the body.
However, there is a type of amyloidosis which is referred to as localised because the amyloid protein is produced and deposited only in one area of the body.
How many and what types of amyloidosis are there?
More than 30 types of amyloidosis, each caused by a different protein. Some types are rare and cause few problems. Each type of amyloidosis is different, requiring different treatment.
Amyloid deposits occur when an amyloid forming protein misfolds to take on a new structure. This new shape allows one misfolded protein to stack upon an other in a “spiral staircase” fashion where each misfolded protein represents a “step” in the staircase. This spiral staircase forms the fibrillar structure called amyloid.
How are the different types of amyloidosis classified?
Amyloidosis is classified according to the main protein that causes that particular type of amyloidosis. The name of each type of amyloid protein consists of “A” for amyloid followed by an abbreviation for the protein that makes up the amyloid deposits. For example, in AL amyloidosis the A stands for amyloid and L for the type of fibril protein, light chain.
Amyloidosis was previously classified as “primary” (occurring on their own) or “secondary” (occurring secondary to another underlying condition), but this terminology was confusing and is no longer used.
The Most Common Types of Amyloidosis are:
AL amyloidosis is caused by abnormal immunoglobulin light chains produced by a small clone of plasma cells in the bone marrow.These plasma cells are usually not cancerous.
About 15% of people with multiple myeloma may also develop AL amyloidosis.
However, most people with AL do not have myeloma, and only rarely do they go on to develop myeloma.
AA amyloidosis occurs when the Serum Amyloid A (SAA) protein increases in some people substantially in response to a long-term inflammatory disorder such as rheumatoid arthritis.
Hereditary ATTR (ATTRv) occurs when a gene mutation causes the body to produce an abnormal form of transthyretin throughout life.
Wild type ATTRwt, previously known as Senile Amyloidosis, occurs when normal or “wild type” transthyretin amyloid deposits in the heart. This is NOT an inherited disease.
AFib (fibrinogen-alpha chain gene mutation) is a less common form of heritable amyloidsosis.
Localised Amyloidosis occurs when the the amyloid protein is produced and deposited in one part of the body only.
NB: Abnormal protein folding is also a feature of Alzheimers disease and Cerebral Amyloid Angiopathy (CAA), however, these conditions are not considered forms of systemic amyloidosis. These diseases are therefore not treated in the Australian Amyloidosis Centres and not mentioned on this web site.
Use the links above for more information on the different types of amyloidosis.
How common is amyloidosis?
In Australia amyloidosis is not a reportable disease so there is no way of knowing how many people have been diagnosed with any of the types of amyloidosis each year. Overall, a recent study has shown that there are 12 new cases per million population diagnosed each year in Australia. It is likely that amyloidosis is more common than this because of undiagnosed cases, particularly of the ATTRwt type.
What are the symptoms of amyloidosis?
Symptoms will depend on the type of amyloidosis and also which tissues and organs are affected and to what degree. Symptoms often mimic those seen in other more common diseases.
Go to individual types of amyloidosis for information on symptoms relevant to each disease.
Due to the rarity of this group of diseases and vagueness of symptoms, diagnosis may be difficult and delayed.
Dr Morie Gertz from the Mayo Clinic advocates that if a patient presents to a doctor with the symptoms listed below, amyloidosis should be considered.
- High levels of protein in the urine, Nephrotic range proteinuria
- Heart failure, Infiltrative cardiomyopathy resulting in heart failure with preserved ejection fraction
- Peripheral or autonomic neuropathy
- Unexplained liver enlargement, hepatomegaly
- Severe bowel motility problems
How is amyloidosis diagnosed?
- There is no single blood test that will diagnose amyloidosis.
- Diagnosis usually begins when a doctor suspects the patient’s symptoms may be due to amyloidosis and starts to run tests or sends the patient to another
- doctor specializing in the treatment of amyloidosis.
- A diagnosis made either through nuclear cardiac scintigraphy or a tissue biopsy of an affected organ
- In the case of tissue biopsy, the specimen is stained with Congo Red dye in the laboratory. If amyloid is present, the biopsy will appear red under normal light and green (apple-green birefringence) under polarized light.
- For ATTR amyloidosis, the diagnosis can often be made by a characteristic tracer uptake pattern with nuclear cardiac scintigraphy, enabling the diagnosis to be reliably made without the need for a tissue biopsy.
- Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis
- This procedure is not reliable in patients with a monoclonal gammopathy.
Treatment
Treatment is very different for each type of amyloidosis and is always geared to the needs and health of the individual patient.
Treatment should ideally be recommended after careful review by experienced amyloidosis treatment teams.
(Click here to view the contact details for treatment clinics in Australia.)
Because of the complex nature of these diseases care is usually offered by a multidisciplinary team as below
- Cardiologists
- Gastroenterologists
- Haematologists
- Immunologists
- Neurologists
- Renal physicians
- Specialized nurses
- Social workers/Counsellors
A patient may not be looked after by all the specialists listed above. This will depend on the type of amyloidosis they have and which organs are affected.
The members of the team may not always work in the same place. e.g. patients visiting a specialized center may see a number of doctors once or twice a year. If the patients live some distance away they may then be looked after by the local G.P and specialist physician with communication being kept between all treating doctors.
