What is Amyloidosis?
Amyloidosis is the name given to a group of rare disorders in which amyloid deposits, consisting of misfolded proteins which are relatively insoluble, deposit and accumulate in tissues and organs of the body. As these deposits progressively build up they interfere with the working of the organs. Without treatment this will eventually leads to organ failure.
Over the past 20 years there has been a greater understanding of these complicated diseases.
Although amyloidosis is still considered incurable, earlier diagnosis. improved technology for diagnosing and typing the diseases, new ways of assessing organ damage and the introduction of new treatments has resulted in many patients experiencing 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 (not a condition you are born with but develops over time)
or
Hereditary (occurs due to a faulty gene passed down through generations).
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. Why different organs are affected in different individuals is yet to be fully worked out.
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?
Over 30 different types of amyloidosis have been identified, each caused by a different protein. Many of these are obscure 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 of shape. 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 formed from misfolded immunoglobulin light chains that are produced by plasma cells in the bone marrow. Usually these plasma cells are benign, but occasionally the amyloid forming light chain protein can be produced by a cancer of plasma cells called Multiple Myeloma. About 15% of patients with Multiple Myeloma will also develop AL amyloidosis. Patients with AL amyloidosis rarely 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 amyloidosis occurs when a gene mutation is inherited, leading to the life-long production of an abnormal or variant protein. The most common types of hereditary amyloidosis are ATTRv (transthyretin gene mutation) and AFib (fibrinogen-alpha chain gene mutation).
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.
Localised Amyloidosis occurs when the the amyloid protein is produced and deposited in one part of the body only.
NB: Alzheimers disease and Cerebral Amyloid Angiopathy (CAA) are not considered to be forms of amyloidosis. These diseases are therefore not treated in the Australian Amyloidosis Centres and not mentioned on this web site.
Click on the different types of amyloidosis for more information.
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 in the USA advocates that if a patient presents to a doctor with the symptoms listed below, amyloidosis should always be considered.
- Nephrotic range proteinuria
- Infiltrative cardiomyopathy resulting in heart failure with preserved ejection fraction
- Peripheral and/or autonomic neuropathy
- Unexplained hepatomegaly
- Dysmotility of the bowel with either pseudo obstruction or steatorrhea
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 is usually made through a tissue or organ biopsy
- The biopsy is stained with the dye Congo red in the laboratory.
- If amyloid is present, the biopsy will appear red under normal light and green (apple-green birefringence) under special polarized light.
- In some circumstances, a DPD bone scan can diagnose heart involvement by ATTR amyloidosis, 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.
Amyloidosis Awareness (narrated by Michael York)
