Hereditary Amyloidosis

There are a number of diseases under the heading amyloidosis which result from the systemic or localised deposition of amyloid fibrils in the extracellular spaces of organs and tissues.

  • Hereditary amyloidosis is a group of rare condition which are less common than (AL) Light Chain amyloidosis.
  • Hereditary amyloidosis is caused by the inheritance of an abnormal/faulty gene (mutation/variant), which leads to life-long production of an amyloidogenic form of a normal protein which deposits in the organs of the body in the form of an amyloid fibril.
  • The faulty gene can be inherited from the father or mother meaning that the presence of just one copy of a mutated gene can cause the disease.
  • Some of those diagnosed will have no known family history.
  • Hereditary amyloidosis is known as an autosomal dominant disease.

Further information on “autosomal dominant inheritance” and “incomplete penetrance” see the tabbed section below.

Are there different types of hereditary amyloidosis?

Hereditary amyloidosis can be divided into:
Non-ATTR hereditary amyloidosis and
Hereditary ATTR (ATTRv) or Hereditary Transthyretin-related amyloidosis.

  • There are well over 100 known genetic variations/
    mutations of hereditary ATTR amyloidosis and about 60 genetic variants/mutations of Non-TTR hereditary amyloidosis.
  • Many variations are very obscure and are not mentioned on this web site.
  • Hereditary ATTR and Afib amyloidosis are the most common of these diseases.
  • All hereditary amyloidosis diseases are systemic, meaning a number of organs can be affected.
  • Organ involved will vary depending on which mutation of hereditary amyloidosis a patient is diagnosed with.
  • Organ damage usually follows a family pattern but there can be variations to this.
  • The age of onset of symptoms for the same mutation may vary by country.

What does ATTR stand for?

  • Different types of amyloidosis are named according to the precursor protein which forms the amyloid fibrils. In ATTRv the A stands for Amyloid and the TTR for transthyretin and the v for variant.
  • Transthyretin (TTR), made in the liver, is the precursor protein which forms the amyloid fibrils.

More information on the naming of Amyloidosis types

The most common types of hereditary ATTR amyloidosis (ATTRv) diseases are:

  • ATTRV30M variant – found mostly in Portugal, Spain, France, Sweden, Japan and descendants of these regions.
  • ATTRV122I variant – seen in 3-4% of African Americans.
  • ATTR T60A variant – seen in people of Irish descent and the most common variant in the UK.

Types of NON-ATTR hereditary amyloidosis with possible organ involvement

  • Afib. Fibrinogen amyloidosis –
    Fibrinogen protein.
    Clinical manifestations: Renal involvement leading to kidney failure.
    Also Visceral, vascular, cardiac (heart), and neurological problems may be experienced.
  • AApoA1. Apolipoprotein A-1 amyloidosis –
    Protein Apolipoprotein A1.
    Characterized by late onset. A systemic disease with predominant renal involvement. Other organs of the body may be affected including the liver, heart, skin and larynx.
  • Apolipoprotein A-2 amyloidosis –
    Protein Apolipoprotein A2
    Chiefly affects the kidneys and is characterized by slowly progressive renal disease.
  • AGel. Gelsolin amyloidosis (also known as Finnish type)
    Protein Gelsolin
    Clinical manifestations include slowly progressive corneal lattice dystrophy, cranial neuropathy, especially affecting the facial nerve, bulbar signs, increased skin fragility, and less commonly peripheral neuropathy and renal failure.

Read the Phillip’s story

  • ALys. Lysozyme amyloidosis –
    Protein Lysozme
    A non-neuropathic form that is systemic. It affects the kidneys, gastrointestinal tract, liver, lymph nodes, and other parts of the body.

More information on ALys. Lysozyme Amyloidosis

Hereditary Lysome Amyloidosis: Spontaneous Hepatic Rupture (15 Years Apart) in Mother and Daughter.

Further information:

Hereditary Amyloidosis

Hereditary Systemic Amyloidosis

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:

  • Echocardiogram.
  • ECG.
  • 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.


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.
Autosomal Dominant Inheritance Pattern

Genetic Testing

Should I have it done and where do I go for advice and the test?

Read the information below from the Health Direct web site and talk with your local doctor of the medical team caring for your relative who has been diagnosed with hereditary amyloidosis.

Health Direct: Genetic Testing

Benefits and Risks of Genetic Testing

Genetic Testing Clinics