Amyloidosis is not a single disease, but an umbrella term for a whole group of diseases. They all have in common what is known as amyloids, deposits of poorly folded proteins in tissue that can be stained like starch under a microscope. About 30 different proteins are known to be able to form amyloids. The amount of these proteins is so large that the body cannot break them down. Protein fibers disrupt the metabolism and function of the organs in which they are stored. How the clinical picture turns out depends on which protein is responsible for amyloid formation.
AL amyloidosis and ATTR amyloidosis (hereditary or acquired form) are common forms, while AA amyloidosis is less common. In addition, a distinction is made between localized amyloidosis, where proteins accumulate in only one place in the body, such as the skin, and systemic amyloidosis, in which amyloid is stored in several organs. In principle, amyloidosis can affect any organ. These are often the heart, kidneys, liver, gastrointestinal tract or nervous system.
Amyloidosis usually progresses over time. The affected organs are gradually losing their function. Depending on the type of amyloid-forming protein, there are different ways to slow the progression of the disease. However, amyloidosis has not yet been cured.
Cause: genetic defect, cancer or inflammatory disease
Hereditary amyloidosis is transmitted from parents to their children. An example is familial ATTR amyloidosis. The protein transthyretin is stored as amyloid in organs such as the heart, kidneys, eyes, tendons and ligaments, as well as in the nervous system. The cause is a gene mutation that leads to an incorrect transthyretin structure.
Hereditary factors play no role in most amyloidoses. AL amyloidosis is usually caused by cancer of the bone marrow and lymph nodes, such as plasma myeloma or non-Hodgkin’s lymphoma of the bone marrow or lymphatic system. Immunoglobulin light chains are subunits of proteins that play a crucial role in the immune system. They are stored in the tissue during AL amyoidosis. Abnormal immune cells in the bone marrow or lymph glands (plasma or lymph cells) produce these abnormal light chains.
AA amyloidosis is caused by a long-term inflammatory disease such as rheumatoid arthritis, Crohn’s disease or ulcerative colitis. Chronic inflammation causes the liver to consistently produce excessive amounts of serum amyloid A (SAA). These proteins can be transformed into AA fibrils, which are deposited mainly in the spleen and later in the kidneys. The liver and gastrointestinal tract, more rarely the heart, may also be affected. AA amyloidosis is not inherited in itself, but occurs in some inherited diseases.
Symptoms: fatigue, weight loss, motor weakness
Although the causes of different amyloidoses are different, they can also cause different symptoms. The symptoms are not the same or the same in all patients. What matters is what type of amyloidosis is present and in which organs insoluble amyloids are stored. In systemic amyloidosis, several organs are affected at the same time, and in local amyloidosis, protein deposits are formed only locally, for example in the skin.
The first symptoms of amyloidosis are often uncharacteristic: fatigue, exhaustion and decreased physical performance also occur in many other diseases.
Symptoms of systemic amyloidosis include:
- Weight loss, nausea, severe fatigue, difficulty sleeping
- motor weakness and sensory disorders in the legs
- Bowel and bladder disorders
- high blood pressure
- sexual dysfunction
- Heart failure with respiratory problems, cardiac arrhythmias, narrowed heart, fainting, sudden cardiac death
- Water retention in the lungs and other tissues
- visual disorders
- renal dysfunction
- thyroid dysfunction
Diagnosis: detection of amyloidosis using a tissue sample
If amyloidosis is suspected, a detailed diagnosis is performed to detect amyloid deposited in the tissue. This initially involves taking a tissue sample (biopsy) from the belly fat, rectal mucosa or affected organ. Sometimes a bone marrow biopsy is also required.
Determining the type of amyloidosis is also important for diagnosis. Because the type of protein that has been stored is crucial to treatment. Other diagnostics include e.g.
- Urine test, eg determination of protein in urine, albumin / creatinine ratio
- Blood test (troponin, BNP, NT-proBNP, blood count, electrolytes, liver values, immunoglobulins)
- Immunohistochemical examination of the removed tissue (staining with Congo red dye, which is bound to amyloid and glows green under a microscope)
- Genetic testing, for example in suspected familial ATTR amyloidosis
- Ultrasound (sonography)
- ECG and cardiac ultrasound (echocardiography)
- Computed tomography (CT)
- Magnetic Resonance Imaging (MRI)
- Lung function test (spirometry)
- Electromyography (EMG) for checking muscle function
- Electroneurography (ENG) for nerve function control
- Skeleton syntax
Treatment: relief of symptoms
Amyloidosis cannot be cured. Rather, the treatment aims to alleviate the symptoms and slow the progression of the disease. The therapy consists mainly in the administration of drugs that are designed to reduce amyloid production. These include, for example
- nonsteroidal anti-inflammatory drugs
- TTR stabilizers
- Antisense oligonucleotide
Various drugs are also used to alleviate the symptoms. In severe cases, liver, heart or a combination of both organs may be necessary.