Organ Damage and Symptoms
- Because hereditary amyloidosis is a systemic disease with the amyloid protein sometimes depositing in similar organs to AL amyloidosis many of the symptoms can be similar to those experienced in AL amyloidosis.
These symptoms may be vague, certainly at first. (Fatigue, swelling ankles, shortness of breath on effort, tingling and pain in hands and feet, diarrhea or constipation, weight loss.)
- Organ involvement and thus symptoms will vary according to the type (mutation/variant) of hereditary amyloidosis.
The most common organs affected in these diseases are the heart, kidneys and nerves, one or all of them.
- In the rare types of Non TTTR hereditary amyloidosis nerve damage is not usually experienced.
- Each family will have its own pattern of organ involvement but there may be variations with in families.
- Symptoms appear at different ages according to the type of hereditary disease. Many symptoms do not appear until middle age.
- The progression of organ damage is often very slow.
Diagnosing Hereditary amyloidosis
If there is already a family history of hereditary amyloidosis suspicions will be raised.
Amyloidosis can only be definitively diagnosed by a tissue or organ biopsy.
- A tissue biopsy involves taking a small piece of tissue from the body, often the fat pad on the tummy or the lip. Sometimes a more invasive biopsy may be taken from the symptomatic organ.
- The biopsy is stained with a dye, Congo red.
- If amyloid is present, the biopsy will appear red under normal light and green (apple-green birefringence) under special polarized light
- Further testing on the biopsy is undertaken to identify the type of of amyloidosis. It is most important that the type of disease is correctly identified as the treatment for each type of amyloidosis is different
The genes of all known types of hereditary systemic amyloidosis can be analysed through a DNA test. Healthy individuals of with a relative diagnosed with a type of hereditary amyloidosis may choose to undergo DNA testing to see whether they carry the gene.
It is advised that this is discussed with a doctor and perhaps seeing a genetic counsellor before undergoing this test.
Other tests to help with diagnosis, assess organ involvement and the degree of damage may include:
- Nerve conduction tests.
- Blood tests.
- Urine analysis.
- DPD Scanning.
- Genetic testing to confirm the diagnosis and analyze the genes associated with the patient’s disease, especially where there is no family history.
- There is no curative treatment available for any type of amyloidosis at this time.
- Chemotherapy has no place in the treatment of hereditary amyloidosis.
- In ATTRv a drug called diflunisal which been proven to stabilize TTR preventing the formation of the amyloid fibrils is available in Australia.
Doxycycline (antibiotic) and Green tea extract have been shown in small studies to break up the amyloid. These medications can have side effects and should only be taken in consultation with
- New treatments that hold hope are at this time being trialed overseas.
Liver transplant may be suggested for a small number of ATTRv patients to slow the production of the precursor protein TTR in the liver.
Kidney and liver transplants may be recommended for patients with organ failure.
Supportive treatments for the organs and tissues damaged by the deposition of the amyloid protein and accompanying symptoms is very important, including dialysis.
Explaining Autosomal Dominance and Incomplete Penetrance in Hereditary Amyloidosis
- Our bodies are made up of billions of cells.
- Each cell contains pairs of chromosomes. These chromosomes carry the genetic information.
- We have 46 chromosomes in total that come in 23 pairs, half from the mother and half from the father. The exception is in men, who have only one X and one Y chromosome.
- The genes that make up these chromosomes provide a map for the bodies development and function. e.g. Colour of our hair and skin are all consequences of the genes we inherit. For this to happen it is important to have all 46 chromosomes with working genes.
- We all have genes that do not function properly. if one is not working the other one usually takes over.
- There are many genetic conditions where if one gene of the pair is not working, the other one cannot compensate, and the person develops the condition with just one non-working copy of the gene. This is known as autosomal dominant inheritance and occurs in hereditary amyloidosis.
- Where an autosomal dominant condition occurs the chance of a person with the condition having a child with that condition, regardless of whether it is a boy or a girl, is 50%. This chance is the same with each pregnancy.
- In many hereditary diseases all people with the mutation will develop the disease. THIS IS NOT SO in hereditary systemic amyloidosis where there is an additional genetic principle known as:
This means that:
- Some people who carry the gene WILL NOT develop any amyloid at all.
- Some people who develop the gene will only develop a small amount of amyloidosis will not produce any clinical symptoms.
- Some people will never inherit the gene and therefore they cannot pass on hereditary amyloidosis to their children.
- Some people will develop hereditary amyloidosis with no knowledge of any family history of the disease.