The following information may help to address your question:
How is hereditary amyloidosis inherited?
The hereditary amyloidoses are inherited in an autosomal dominant manner. This means that one altered copy of the disease-causing gene (called a mutation) in each cell is sufficient to cause the disease. The disease-causing mutation can be inherited from a parent or it can occur for the first time in an individual. Each child of an individual affected with hereditary amyloidosis has a 50% (1 in 2) risk to inherit the disease-causing mutation and a 50% chance of not inheriting the mutation. However, not all individuals with a mutation in a gene that causes hereditary amyloidosis will develop signs and symptoms of the disease.
Last updated: 9/16/2011
What are the signs and symptoms of hereditary amyloidosis?
There is a broad range of symptoms and age of onset for individuals with different types of hereditary amyloidosis. The extent of organ
involvement may range from very localized amyloid deposition to general systemic (wide-spread) involvement. When amyloid is abnormally deposited within the body, it leads to dysfunction of the organs involved. In many cases, the specific gene and/or mutation involved determines which organs are affected. Generally, the type of protein
, the tissue
in which it is deposited, and the amount of deposition determines the signs and symptoms present in each individual.
The course of the disease may be similar among members of the same family, but this is not always the case. There have been instances where affected individuals remain without symptoms, have late-onset, or more severe disease than other affected family members.
The following is a brief description of the reported features in several forms of hereditary amyloidosis:
- Familial transthyretin amyloidosis - Amyloid deposits in the nerves of the peripheral nervous system result in a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system (which controls involuntary body functions such as blood pressure, heart rate, and digestion) as well as the central nervous system (brain and spinal cord) may also be affected. Other areas of the body affected may include the heart, kidneys, eyes, and gastrointestinal tract.
- Apolipoprotein A-1 amyloidosis - This form is characterized by late onset and systemic disease with predominant renal involvement. Other parts of the body affected include the liver, heart, skin and larynx.
- Apolipoprotein A-2 amyloidosis - This type chiefly affects the kidneys and is characterized by slowly progressive renal disease.
- Gelsolin amyloidosis (also known as Finnish type) - Characteristics include slowly progressive cranial neuropathy (damage to the cranial nerves), peripheral neuropathy, lattice corneal dystrophy, and skin disease.
- Fibrinogen amyloidosis - This is a systemic type with renal failure being prominent; there is also vascular, cardiac (heart), and neurologic involvement.
- Lysozyme amyloidosis - This is a non-neuropathic form that is systemic and affects the kidneys, gastrointestinal tract, liver, lymph nodes, and other parts of the body.
- Cystatin C amyloidosis - This form mainly affects the brain and is characterized by multiple strokes and mental status changes beginning in the second or third decade of life. Many affected individuals die by 40 years of age.
Last updated: 9/16/2011
How is hereditary amyloidosis diagnosed?
In the case of hereditary amyloidoses, the existence of a family history
or similar illness is of great assistance in diagnosing the condition. However, not everyone with a mutation
in a gene
associated with hereditary amyloidosis will develop symptoms. Additionally, symptoms of the disease typically do not appear until older age and the condition may have been misdiagnosed in other affected family members. For these reasons, the absence of a family history may be misleading.
The diagnosis of amyloidosis is usually made by performing a tissue biopsy
and staining the tissue with Congo red stain to detect the presence or absence of amyloid deposits. The biopsy may be from any affected organ, but biopsying the rectal mucosa
generally results in better detection of the following hereditary amyloidoses: transthyretin amyloidosis, apolipoprotein AI amyloidosis, fibrinogen Aα-chain amyloidosis (A Fib), and apolipoprotein AII amyloidosis (A ApoAII).
Additionally, when a hereditary amyloidoses is suspected, genetic testing
may be able to confirm a diagnosis. It is important to note that genetic testing may not be available for all types of hereditary amyloidoses. For those individuals interested in pursuing genetic testing, we recommend scheduling a genetics consultation
to determine whether genetic testing would be appropriate and available.
Last updated: 9/16/2011
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Last updated: 7/15/2016
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