Introduction to Amyloidosis
Amyloidosis is a rare disease caused by abnormal deposition and accumulation of proteins in the tissues of the body. The most common type of hereditary amyloidosis is transthyretin amyloidosis (ATTR), a condition in which the amyloid deposits are most often made up of the transthyretin protein which is made in the liver.
ATTR amyloidosis means A for Amyloid and the TTR is short for the protein “transthyretin.” ATTR is one term that represents different kinds of mutations in a TTR gene that is inherited. That gene mutation makes the transthyretin unstable, so amyloid protein misfolding occurs. ATTR amyloidosis is caused by a genetic mutation (change within a gene). ATTR amyloidosis can be either hereditary (hATTR) or acquired (non-hereditary).
hATTR amyloidosis had been previously referred to as transthyretin familial amyloid polyneuropathy (TTR-FAP) or familial amyloid cardiomyopathy (TTR-FAC), deriving its name from the most predominant clinical presentation.3,4
Whereas the nonhereditary, wild-type ATTR amyloidosis primarily affects the heart, hATTR amyloidosis affects multiple organs and body systems, such as the heart, nervous system, gastrointestinal tract, and kidney.
The child of a parent with this mutation will have a 50% chance of inheriting the mutation. However, this does not necessarily mean that the child will develop the condition. It’s important to understand your family health history and speak with your doctor about how hATTR amyloidosis runs in the family. Other examples of hereditary amyloidosis include, but are not limited to, apolipoprotein AI amyloidosis (A ApoAI), gelsolin amyloidosis (A Gel), lysozyme amyloidosis (A Lys), cystatin C amyloidosis (A Cys), fibrinogen Aα-chain amyloidosis (A Fib), ATTR T60A and apolipoprotein AII amyloidosis (A ApoAII). Most types of hereditary amyloidosis are inherited in an autosomal dominant manner. Treatment is focused on addressing symptoms of organ damage and slowing down the production of amyloid when possible through methods such as liver transplants.
Amyloid deposits are primarily made up of protein fibres known as amyloid fibrils. These amyloid fibrils are formed when normally soluble body proteins aggregate (clump together), and then remain in the tissues instead of safely going away. About 30 different proteins are known to form amyloid deposits in humans.
Amyloid deposits cause disease by gradually accumulating within organs and thereby disrupting the structure and damaging the function of the affected tissues. In some cases, previously healthy organs can be substantially replaced by extensive amyloid deposits.
Amyloidosis is usually a systemic disease. This means that many body organs and systems may be affected. There are many forms of amyloidosis, some of which are acquired, including: AL (immunoglobulin light chain)/ AL amyloidosis; Amyloid A (AA) amyloidosis/ AA amyloidosis, dialysis-related amyloidosis (DRA); wild-type ATTR (ATTRwt) amyloidosis and organ-specific amyloidosis. Unlike these acquired forms of the disease, hATTR amyloidosis is hereditary meaning it can be passed down generationally/ hereditary amyloidosis.
Organs that may be affected by systemic amyloidosis include the:
- liver and spleen
- nervous system
- gut and tongue
- bones and joints- especially the wrists
- blood vessels and clotting system
It often impacts quality of life:
- Decreased mobility
- Gastrointestinal issues
- Trouble with self-care
- Difficulty performing usual activities
Sometimes the organs affected and the patient’s symptoms are related to the type of amyloid fibril, but in many forms of amyloidosis there is little or no clear correlation between the fibril protein and the clinical findings. Nevertheless, in order to provide appropriate treatment, it is always essential for doctors to identify the amyloid fibril protein.
Less frequently, localised deposits of amyloid may appear just in one area, such as the airways, skin or bladder.
Amyloid deposits can form in almost any tissue of the body. Therefore the symptoms and signs of the disease can vary greatly and are often vague and not specific. Many patients undergo extensive testing and see several doctors before the diagnosis is made.
Once a doctor suspects that amyloidosis may be present it is possible to confirm the diagnosis quite easily. However, since amyloidosis is rare and the symptoms are so non-specific, it is not a diagnosis that springs to mind readily for many doctors and missed diagnosis and delayed diagnosis of amyloidosis are common.
The varying symptoms of hATTR amyloidosis
This is not a complete list of symptoms that may be experienced with hATTR amyloidosis.
At present, the SAP scan housed at the National Amyloidosis Centre at the Royal Free Hospital in London is the only technique available to pinpoint the exact location and amount of amyloid within the body’s organs.
Sequential SAP scans from a patient with AL amyloidosis. In 2005 the scan showed significant deposits in the liver and spleen. The scan in 2009 showed considerable shrinkage of the deposits after a good response to treatment. In 2011 there was a relapse and the scan showed amyloid building up, this time in the kidneys.
Reproduced from: Journal of Immunological Methods 384;Issues 1-2, 2012, 92-102
Recent years have seen important strides forwards in treatment and the outlook for patients diagnosed with amyloidosis today is far better than it was even a few years ago. Twenty years ago the life expectancy of patients diagnosed with amyloidosis was usually only a few months or years, whereas now it is often 10 years or more.
Currently available treatments differ considerably for the different types of amyloidosis, but they all focus on reducing the availability of the proteins which form amyloid fibrils (precursor proteins). In many cases patients benefit considerably from these treatments, with regression of amyloid deposits once the precursor supply is stopped and subsequent substantial health improvements.
Amyloidosis is never contagious and it is not cancerous, although AL amyloidosis is treated in a similar fashion to a bone marrow cancer called myeloma.
*most information taken from