Amyloidosis: what is it and why does it arise, what symptoms does it have?

Amyloidosis: what is it and why does it arise, what symptoms does it have?
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Amyloidosis is a disorder of metabolism and accumulation of amyloid in the body. Amyloid is one form of several proteins. Why does this disease occur and how is it manifested or treated?


Amyloidosis is a rare disease that is caused by an abnormal protein called amyloid. It occurs when amyloid builds up in the organs, interfering with their normal function.

Amyloid is not normally found in the body, but can be made up of several different types of proteins. The organs most affected by amyloidosis include the heart, kidneys, liver, spleen, nervous system and digestive tract.

Some types of amyloidosis occur in association with other diseases. These types of amyloidosis can be "cured" by proper treatment of the underlying disease.

Some types of amyloidosis are severe, progress rapidly and lead to life-threatening organ failure.

Treatment involves chemotherapy, very similar to that used for cancer. In individual cases, organ or stem cell transplantation is an option.

Amyloidosis is a relatively rare disease.

It is caused by the accumulation of a difficult-to-solve protein called amyloid in the organs of the human body. The accumulation of this protein in the tissues of the organs causes damage to them, thereby interfering with their normal function.

Amyloid is an insoluble protein that has the character of fibrils. Its specific structure, which is similar to a folded sheet, protects this protein from proteolysis (breaking down into smaller subunits - dissolution).

There are currently more than 30 known types of proteins that can cause amyloidosis, i.e. accumulation in tissues. These so-called amyloidogenic proteins accumulate extracellularly, i.e. between cells, not inside them.

Amyloidosis is a rare disease.
It affects approximately 5-12 patients per 1 million people each year.
It is more common in men.


There are several different types of amyloidosis.

Some types are hereditary. However, acquired forms of amyloidosis are much more common and may be caused by external factors such as chronic inflammatory diseases or years of dialysis.

In most cases, amyloidosis affects multiple organs, but there are also several types that affect only one part of the body.

Types of amyloidosis

Several forms of this disease are known.

AL amyloidosis

Also called primary amyloidosis, this is the most common type of amyloidosis in developed countries.

It accounts for up to 70% of all acquired amyloidoses.

It is caused by the deposition of free light chains of immunoglobulins, which are the products of clonal plasma cells. In 20% of cases, primary amyloidosis is associated with haemato-oncological diseases such as multiple myeloma or Waldenström's macroglobulinaemia.

This form mainly affects the heart, kidneys, liver and nervous system.

AA amyloidosis

Also referred to as secondary amyloidosis or reactive amyloidosis because it is usually caused by long-term inflammatory disease.

Often these are rheumatic diseases such as rheumatoid arthritis, ankylosing arthritis or juvenile arthritis.

AA amyloidosis can also be caused by chronic intestinal inflammation, osteomyelitis, chronic respiratory diseases or non-healing skin defects.

Improved treatment of chronic inflammatory diseases has led to a sharp decline in the number of cases of AA amyloidosis.

In the past, AA amyloidosis accounted for up to 45 % of all cases of amyloidosis, but nowadays it occurs in approximately 6 % of cases in developed countries.

It most commonly affects the kidneys, liver and spleen.

Hereditary amyloidosis (familial amyloidosis)

This is a hereditary disease.

The disease is caused by the accumulation of amyloid protein, which is a defective transthyretin.

A genetic mutation causes a change in the structure of this protein, specifically the replacement of one amino acid with another. Such a change destabilises the entire protein molecule, which then forms a beta-folded sheet structure - i.e. amyloid.

The mutation is present from birth. The disease itself begins to manifest itself between the ages of 20 and 50.

This type of amyloidosis mainly affects the nervous system, heart and kidneys.

Senile amyloidosis

This is a type of amyloidosis that also results from the deposition of transthyretin, but unmutated, so-called native or wild-type transthyretin. This protein, which is formed in the liver, is normal and not subject to mutation. However, for unknown reasons, it begins to form an amyloid structure and thus becomes undegradable.

It predominantly affects men in their 70s.

The clinical symptoms are most pronounced in the heart. It also causes carpal tunnel syndrome.

Localised amyloidosis

It is characterised by affecting only one site or organ of the body.

It usually has a better prognosis than the aforementioned types of amyloidosis that affect several organ systems.

Typical sites of involvement are the bladder, skin, throat or lungs.

Risk factors

The main factors that can increase the risk of amyloidosis include:

  • Advanced age - amyloidosis predominantly occurs between the ages of 60 and 70, although it can occur earlier.
  • male gender
  • chronic infectious or inflammatory diseases (especially for AA amyloidosis)
  • family history of the disease (hereditary types of amyloidosis)
  • dialysis, which filters out large proteins from the blood, is rarer with more modern dialysis technologies
  • black race


Symptoms of amyloidosis may not manifest for a long time or may be mistaken for other diseases.

A correct diagnosis can only be confirmed in advanced disease when numerous organs of the body are affected by amyloid.

Typical symptoms of amyloidosis include:

  • Swelling of the ankles and feet
  • Severe fatigue and weakness
  • Shortness of breath with minimal exertion
  • Inability to lie in bed due to shortness of breath
  • Numbness, tingling or pain radiating to the hands or feet, especially pain in the wrists (carpal tunnel syndrome)
  • Diarrhoea, possibly stools with blood or, conversely, constipation
  • Unintentional weight loss of more than 5 kilograms
  • Enlarged tongue, which may be wavy at the edges (caused by impacted teeth)
  • Change in skin quality, e.g. thickened skin
  • Light bruising
  • Red-purple spots around the eyes
  • Irregular heartbeat
  • Difficulty swallowing

Affection of the heart

Accumulated amyloid in the heart causes a decrease in volume when filling the chambers between heartbeats.

In practice, this means that with each heartbeat, the chambers fill less and less. Therefore, the volume of blood that is pumped into the body is less.

The result is rapid fatigue, shortness of breath, chest pain and inefficiency.

If amyloidosis affects the places in the heart that produce electrical impulses, changes in heart rhythm, fibrillation or tachycardia can occur. Such an affection is potentially life-threatening.

Kidney damage

Amyloid can deposit in the kidneys, damaging the very delicate filtration system.

The result is increased leakage of proteins that do not normally enter the urine because the body saves them.

The kidneys' ability to remove waste products that are produced during nutrient metabolism is also reduced. The end result is kidney failure and the need for the patient to be dialysed.

Symptoms from the nervous system

A common symptom of amyloidosis is pain.

The pain may be accompanied by numbness or tingling in the fingers, a burning sensation in the toes or feet.

Amyloid can also affect the nerves that innervate the intestines, such as the bowels. Therefore, patients have problems with frequent diarrhoea or, conversely, constipation.


Amyloidosis is a diagnosis that can be overlooked for years.

The symptoms of the disease are very similar to those of other more common diseases. Therefore, the rarer amyloidosis is not thought of immediately when a patient first visits with difficulty.

Early diagnosis is essential for the future prognosis of the disease, as rapid therapeutic intervention prevents further organ damage. Accurate diagnosis in determining the type of amyloidosis is also very important, as treatment varies greatly depending on the type of amyloidosis.

Laboratory tests

Blood and urine tests can reveal the presence of the abnormal protein, but in many cases conventional peripheral blood and urine electrophoresis will not detect the presence of monoclonal immunoglobulin because of its very low concentration.

Bone marrow examination is more sensitive.

Genetic testing

To establish the diagnosis of hereditary amyloidosis, genetic testing of blood is performed. The presence of the most common mutations of the amyloid genes is monitored.


Tissue histology is crucial in establishing a correct diagnosis. A tissue sample is taken during a non-targeted biopsy (randomly selected organs with more frequent involvement), e.g. from the subcutaneous fat around the umbilicus, salivary glands, tongue or rectum.

If the result is negative and amyloidosis is suspected to persist, a targeted biopsy (organs that we know are affected by the disease but do not know what disease) is required from the affected organs, i.e. liver, kidney, nerve, heart, etc.

Specific tissue testing can help determine the exact type of amyloid deposit. For example, staining the sample with Congo red and then viewing the sample in a polarizing microscope is used.

A positive specimen shows so-called dichroism, i.e. a change in colour with a change in the angle of incident light.

Imaging examination

From imaging examinations of organs we can assess the degree of damage. For example, MRI of the heart is used.


The course of this serious disease depends on the provoking cause of the disease.

Amyloidosis is a gradually progressive disease, with a creeping onset and a difficult to recognize clinical syndrome.

With more severe organ damage, the disease is at an advanced stage where it is difficult to reverse its prognosis.

The prognosis depends on the type of amyloidosis and the patient's adequate response to treatment.

If left untreated, systemic amyloidosis is often fatal.

Time and survival rates depend on the degree and number of organs affected.

In terms of morbidity, cardiac involvement is the most serious.

How it is treated: Amyloidosis

Amyloidosis treatment: drugs, chemotherapy to transplantation

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Manifestations and symptoms of the disease - video

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Interesting resources

  • - Dialysis amyloidosis, MUDr. Radoslav Roman, Assoc., MUDr. Kamil Ševela, CSc., MUDr. Darja Krusová, Ph.D., MUDr. Jan Svojanovský, Ph.D., prof. MUDr. Miroslav Souček, CSc., II. internal medicine clinic, St. Anne's Hospital in Brno, MUDr. Lukáš Pazourek, Orthopaedic clinic, St. Anne's Hospital in Brno
  • - Systemic amyloidosis, Lenka Zahradová, MUDr., Ph.D., Department of Haematooncology, University Hospital Ostrava, Ostrava
  • - Hereditary amyloidosis with transthyretin deficiency and its neurological manifestations, Jana Laštovičková, M.D., Department of Neurology, Regional Hospital Kolín
  • - Amyloidosis
  • - Amyloidosis
  • - The Amyloidoses: Clinical Features, Diagnosis and Treatment