My Amyloidosis

Amyloidosis

(from the National Amyloidosis Centre in London)
The term amyloidosis describes a group of disorders caused by abnormal folding, aggregation and accumulation of certain proteins in the tissues, in an abnormal form known as amyloid deposits. These deposits are composed of abnormal protein fibres, the so-called amyloid fibrils that accumulate more quickly than they are cleared away, and which progressively interfere with the structure and function of affected organs throughout the body. Normal healthy proteins are cleared away at about the same rate that they are produced, but proteins that have formed amyloid are broken down only very slowly.

About 23 different proteins have been found to form amyloid in man, but only a few are associated with clinically significant disease. Amyloidosis is classified according to the protein that forms the amyloid fibrils, and the clinical picture and symptoms can differ greatly between one amyloid type and another. The proteins that cause the two most common types of systemic amyloidosis (i.e. the types that can affect many parts of the body) are produced in the presence of other disorders. Patients with systemic AL amyloidosis (formerly known as primary amyloidosis) have an underlying bone marrow disorder, and patients with systemic AA amyloidosis (formerly known as secondary amyloidosis) have some form of long standing inflammatory disorder. Other types of amyloidosis have a genetic basis, most of which can now be identified by DNA tests.

Amyloid deposits can accumulate virtually anywhere in the body or can remain localised to one particular organ or tissue. Symptoms occur as a result of progressive damage to affected organs and tissues, for example the kidneys or heart, and may vary greatly from patient to patient.

Although various specific anti amyloid drugs are under development, none as yet has been introduced into routine clinical practice. However, available treatments for the various conditions that underlie amyloidosis can stabilise or improve organ function, and may greatly improve the outlook. Contrary to previous beliefs, we have shown that amyloid deposits often gradually diminish in patients whose underlying conditions respond to treatment.

Sometime truly localised forms of amyloidosis can cause significant disease, for example in the airways, skin or bladder, and patients on long-term dialysis may develop amyloid in the bones and joints. Localised amyloid deposits composed of a protein called Aβ occur in the brains of patients with Alzheimer’s disease, but it is not known whether they are the cause of the disease. Fortunately, the brain is almost never directly involved in systemic amyloidosis.

The National Amyloidosis Centre offers a clinical service for patients with all types of amyloidosis other than Alzheimer’s disease, although its research programme does include the latter. There are three main types of systemic amyloidosis – AA, AL and hereditary - which are described in more detail below. Systemic AA amyloidosis occurs in up to 5% of patients with chronic inflammatory diseases, most commonly rheumatoid arthritis, and systemic AL amyloidosis occurs in a small proportion of patients who have either multiple myeloma (a bone marrow cancer) or, much more commonly, a non malignant disorder of the bone marrow. Unfortunately, both AA and AL amyloidosis cause rather non-specific symptoms, and diagnosis is often delayed until many investigations, often culminating in a tissue biopsy, have been performed. Systemic AL amyloidosis is now 2 or 3 times more common than AA type in the UK, and together there are probably about 500-1000 new cases each year.

Filed under: What is Amyloidosis on October 28th, 2008