Glossary

AMYLOIDOSIS

The term amyloidosis identifies a heterogeneous collection of disorders characterized by a deposit of abnormal proteins occurring in various organs and tissues. Such protein deposits occur in the form of fibrils and are referred to as amyloids.  The damage caused by amyloids to the various organs and tissues is determined by its progressive accumulation. These forms of amyloidosis are rare pathologies, yet serious ones with a very high mortality rate. The distribution of amyloids can be either local or systemic. What determines the differences between different types of amyloidosis boils down to several proteins, which for reasons that are still unknown, can mutate their structure; furthermore, they are determined by the different points in which the amyloid tends to concentrate. Hence, it goes without saying that amyloidosis can occur under a variety of different clinical picture. Furthermore, it also follows that the mismatches between clinical picture and symptomatology may cause considerable difficulties in terms of allowing an early diagnosis; this timeliness is regarded as a key factor in addressing the pathology.

 

Amyloidosis: the main groups

The most important groups of amyloidosis are the following:

• primary AL amyloidosis

• secondary AA amyloidosis

• hereditary amyloidosis.

 

Primary AL amyloidosis – AL amyloidosis (light-chain amyloidosis) is characterized by deposits of monoclonal immunoglobulin light chains, proteins that are produced within the bone marrow; these immunoglobulins are produced in order to protect the body from pathological processes. For yet unknown reasons, once these immunoglobulins have carried out their function, they do not dissolve but rather transform into amyloid fibrils, which are transported by the bloodstream and progressively build up in various organs and tissues.

 

Secondary AA amyloidosis – AA amyloidosis is a type of amyloidosis that is secondary to several other diseases. The protein that characterizes this type of amyloidosis is the SAA (Serum Amyloid A), a protein that is produced during acute phases of chronic diseases such as rheumatoid arthritis.

In some cases, primary amyloidosis treatment can slow down the progression of the disease, possibly even halting it. The organs that are generally more seriously affected within this form of amyloidosis are the kidneys, with the possibility of proteinuria, nephrotic syndrome and renal failure. Other organs that may be affected by this type of amyloidosis, though less severely, are liver and spleen. In very rare cases, also the heart may be affected.

 

Hereditary Amyloidosis – several proteins are involved in the development of hereditary amyloidosis; the mutation of the latter give rise to different types of hereditary amyloidosis. Among the different types of hereditary amyloidosis, transthyretin amyloidosis (TTR amyloidosis, MIM 176300) occurs with greater frequency. Transthyretin (TTR) is a protein that is mainly secreted by the liver. It is involved in the transport of thyroid hormones (thyroxine and RBP, retinol-binding protein). Clinically, this type of amyloidosis generally involves the peripheral nervous system as well as the autonomic nervous system. TTR amyloidosis has an autosomal dominant transmission (there is a 50% chance of disease transmission; if the children do not inherit the disease, there is no risk that they can pass it on to the next generation). TTR amyloidosis shares some similarities with AL amyloidosis: however, unlike the latter, TTR amyloidosis is less aggressive and chances of survival are greater. Another type of hereditary amyloidosis is apolipoprotein AI amyloidosis (AApoAI, MIM 107680). In this type of amyloidosis, amyloid accumulation generally involves organs such as heart, liver and kidneys; this leads to a clinical picture respectively of cardiomyopathy, liver disease and kidney disease.

 

Diagnosis of Amyloidosis

In order to diagnose amyloidosis, amyloid deposits have to be identify by means of specific staining of a tissue sample. To this end, a peri-umbilical fine needle aspiration is generally performed, a simple and painless test with a sensitivity approaching 80% (in the systemic forms of amyloidosis). Where the needle aspiration fails to diagnose amyloidosis, a biopsy of the labial minor salivary gland may be performed in order to clear any remaining concerns. Depending on the situation, a biopsy may be required on organs suspected of being affected by amyloidosis. If the diagnostic tests confirm the presence of amyloid, it is necessary to identify the protein which causes deposits in order to determine which type of amyloidosis has affected the subject. The identification of the protein is a critical step with regard to the treatment, since the latter varies with the type of amyloidosis.

 

 

See also:

Glossary

Presentation n. 13