WHAT IS AMYLOIDOSIS?
are a group of diseases that result from a protein folding abnormality that causes deposits of amyloid fibrils in organs throughout
the body and leads to organ dysfunction.
three major systemic types, each caused by a different mis-folded protein. All
are very different.
common is AL, A
for amyloid and L for the Light chain that is the abnormal part of any antibody
made in the bone marrow in patients with this disease.
type is AA in which the amyloid protein comes from serum amyloid A, a protein
that is elevated in inflammatory disease.
forms comprise the last category and are characterised by deposits of a variety of different mis-folded proteins.
was first described in the 19th century, but only in recent years have significant advances been made in identification
of types and their diagnosis and treatment.
PRIMARY AMYLOIDOSIS (AL)
antibody light chain produced in the bone marrow by a plasma cell is the cause of primary amyloidosis.
of this type can occur occasionally with multiple myeloma, also a disease of plasma cells.
deposits are the light chain protein and often occur in multiple organs in a short period of time. Without treatment this disorder can be serious and sometimes fatal.
The survival rates can vary for each patient.
most often involved in AL amyloidosis include the heart, kidneys, nervous system, and gastrointestinal tract.
may include shortness of breath, fatigue, oedema (swelling of ankles and legs) dizziness upon standing, a feeling of fullness
in the stomach, diarrhoea, weight loss, enlarged tongue, numbness of the legs and arms, and protein in the urine (often marked
by frothing or bubbles).
is the most common type and is usually treated with chemotherapy and/or SCT to kill the abnormal plasma cells, or to slow
production of the abnormal light chain. Trials of different classes of drugs
for treatment are currently underway.
SECONDARY AMYLOIDOSIS (AA)
Amyloidosis is caused by a long term serious chronic infection such as TB or osteomyelitis, or inflammatory disease such as
rheumatoid arthritis or familial Mediterranean fever.
deposits in this type of amyloidosis are made up of AA protein, a protein that is markedly elevated in the body during inflammation. The disease progression is usually slow, and treatment of the underlying chronic infection
or inflammatory disease can slow down or stop the progression of further amyloid deposits.
Survival is measured in years.
(AA) amyloidosis the organs most involved is the kidneys, but GI tract, liver and heart can be involved as the disease progresses. Symptoms include protein in the urine, oedema, weight loss and fatigue.
HEREDITARY OR FAMILIAL AMYLOIDOSIS
mutations of several different genes lead to familial amyloidosis.
common is an inherited transthyretin (TTR) mutation. This form is called Amyloid
100 different mutations of TTR that can cause amyloidosis. Some mutations can
occur in many ethnic groups, while others are, thus far, very rare, occurring in only one or two families.
the abnormal protein is present from birth, disease usually begins in mid-life. Symptoms
are a little different for each mutation, and include neuropathy, gastrointestinal dysfunction, cardiomyopathy, vitreous opacities,
and renal disease.
that may have mutations leading to Amyloidosis are apolipoprotein A-I, apolipoprotein A-II, fibrinogen, lysozyme and gelosin.
an inherited form known as “wild type transthyretin” that strikes approximately 4% of the African American population
in the heart at mid-life.
of affected parents have a 50% chance of inheriting the abnormal gene. DNA testing
is recommended when the child becomes an adult.
So far this
page lists the more common types of this rare disease, but there are localised versions, cerebral, and others.
SYMPTOMS OF AMYLOIDOSIS
is difficult, because amyloidosis resembles other medical problems. Symptoms
can include unexplained weight loss, leg swelling (oedema), shortness of breath and fatigue; occasionally one can look like
one has black eyes (purpura).
Amyloidosis may also have arm and leg numbness (peripheral neuropathy), carpal tunnel symptoms, changes in their nails and
foamy urine. Swallowing problems can also be a part of the puzzle of Amyloidosis
(enlarged tongue). With early diagnosis, amyloidosis can be treated.
of amyloidosis is made by a tissue biopsy that is treated with a special stain, Congo red and examined under polarised light
microscopically. There are other non invasive tests available such as the Serum
FLC Assay Test. Further testing is required to determine the amyloid type.
will first determine if the amyloid is of the most common AL
type by checking for an abnormality of plasma cells in the bone marrow or light chains in the blood and urine. To determine other types more sophisticated pathology or genetic testing is required.
at a centre of excellence is helpful to receive the proper diagnosis and treatment.
In the UK this is at the National Amyloidosis Centre, based at the
Royal Free Hospital,
depends on which type of amyloid protein is present in the body, where it is being deposited, and how it is affecting organ(s). It may range from pills, to injected chemotherapy, to stem cell transplants. Clinical trials are available to patients for some types. On other occasions, organ transplants are performed.