Amyloidosis is a rare disease that results from the build up of misfolded proteins known as amyloids. When proteins that are normally dissolvable in water fold to become amyloids, they become insoluble and deposit in organs or tissues, disrupting normal function. The type of protein that is misfolded and the organ or tissue in which the misfolded proteins are deposited determines the clinical manifestations of amyloidosis.
There are four main types of amyloidosis, each due to the deposition of a specific protein. The most common type is AL amyloidosis, caused by the deposition of light chain proteins produced by plasma cells in different disease states.〔 http://www.amyloidosis.org/facts/al/ AL Amyloidosis〕 The second most common is AA amyloidosis due to the accumulation of S amyloid A protein or SAA, which occurs in association with chronic infectious - e.g. tuberculosis - or inflammatory illnesses such as rheumatoid arthritis. The third and fourth types are due to the deposition of respectively, a genetically defective or normal form of a protein called transthyretin. Other minor forms of amyloid are also known.
== Signs and symptoms ==
The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. The kidney and heart are the most common organs involved.
Amyloid deposition in the kidneys can cause nephrotic syndrome, which results from a reduction in the kidney's ability to filter and hold on to proteins. The nephrotic syndrome occurs with or without elevations in creatinine and blood urea concentration,〔 two biochemical markers of kidney injury. In AA amyloidosis the kidneys are involved in 91-96% of people,〔 symptoms ranging from protein in the urine to nephrotic syndrome and rarely renal insufficiency.
Amyloid deposition in the heart can cause both diastolic and systolic heart failure. EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction. On echocardiography the heart shows restrictive filling pattern, with normal to mildly reduced systolic function.〔 AA amyloidosis usually spares the heart.〔
People with amyloidosis do not get central nervous system involvement but can develop sensory and autonomic neuropathies. Sensory neuropathy develops in a symmetrical pattern and progresses in a distal to proximal manner. Autonomic neuropathy can present as orthostatic hypotension but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety.〔
Deposition of amyloids in the liver can lead to elevations in serum aminotransferases and alkaline phosphatase, two biomarkers of liver injury, which is seen in about one third of people.〔 Liver enlargement is common. In contrast, spleen enlargement is rare, occurring in 5% of people. Splenic dysfunction, leading to the presence of Howell-Jolly bodies on blood smear, occurs in 24% of people with amyloidosis.〔 Malabsorption is seen in 8.5% of AL amyloidosis and 2.3% of AA amyloidosis. One suggested mechanism for the observed malabsorption is that amyloid deposits in the tips of intestinal villi (fingerlike projections that increase the intestinal area available for absorption of food), begin to erode the functionality of the villi, presenting a sprue-like picture.〔
A rare development is a susceptibility to bleeding with bruising around the eyes, termed "racoon-eyes". This is caused by amyloid deposition in the blood vessels and a reduced activity of thrombin and factor X, two clotting proteins that lose their function after binding with amyloid.〔
Amyloid deposits in tissue and causes enlargement of structures. Twenty percent of people with AL amyloidosis have an enlarged tongue, that can lead to obstructive sleep apnea, difficulty swallowing, and altered taste.〔 Tongue enlargement does not occur in ATTR or AA amyloidosis.〔 Enlarged shoulders, "shoulder pad sign", results from amyloid deposition in synovial space. Deposition of amyloid in the throat can cause hoarseness.〔 Aβ2MG amyldoisis (Hemodialysis associated amyloidosis) likes to deposit in synovial tissue causing chronic synovitis which can be lead to repeated carpal tunnel syndrome.〔
Both the thyroid and adrenal gland can be infiltrated. It is estimated that 10-20% of individuals with amyloidosis have hypothyroidism. Adrenal infiltration may be harder to appreciate given that its symptoms of orthostatic hypotension and low blood sodium concentration may be attributed to autonomic neuropathy and heart failure.〔
"Amyloid deposits occur in the pancreas of patients with diabetes mellitus, although it is not known if this is functionally important. The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or amylin. This is stored with insulin in secretory granules in B cells and is co secreted with insulin". (Rang and Dale's Pharmacology, 2015).
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