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Amyloidosis
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In medicine, amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. A protein is described as being amyloid if, due to an alteration in its secondary structure, it takes on a particular aggregated insoluble form similar to the beta-pleated sheet. [1] Symptoms vary widely depending upon the site of amyloid deposition. Amyloidosis may be inherited or acquired. [2]

Amyloidosis
Classification and external resources

Interaction Help About Wikipedia Community portal Recent changes Contact Wikipedia Contents [hide] 1 Classification of amyloid 2 Pathogenesis 3 Classification 4 Symptoms 5 Diagnosis 6 Alternative classifications Toolbox What links here Related changes Upload file Special pages Permanent link Cite this page 7 Additional images 8 References 9 External links

Classification of amyloid

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The modern classification of amyloid disease tends to use an abbreviation of the protein that makes the ICD-10 E85. majority of deposits, prefixed with the letter A. For example amyloidosis caused by transthyretin is 277.3 ICD-9 termed "ATTR." Deposition patterns vary between DiseasesDB 633 patients but are almost always composed of just one med/3377 med/3888 eMedicine amyloidogenic protein. Deposition can be systemic D000686 MeSH (affecting many different organ systems) or organspecific. Many amyloidoses are inherited, due to mutations in the precursor protein. Other forms are due to different diseases causing overabundant or abnormal protein production - such as with over production of immunoglobulin light chains in multiple myeloma (termed AL amyloid), or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA amyloid). Out of the approximately 60 amyloid proteins that have been identified so far,[3] at least 36 have been associated in some way with a human disease. [4]

Micrograph showing amyloid deposition (red fluffy material) in the heart (cardiac amyloidosis [disambiguation needed ] ). Congo red stain.

Pathogenesis
When a native cell creates a protein, it could either make the actual protein or protein fragments. These fragments could come and join together to form the actual protein. This protein can sometimes regress into the protein fragments. This process of "flip flopping" happens a lot in certain proteins, especially the ones that cause this disease. The fragments or actual proteins are

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at risk of mis-folding as they are synthesized, to make a bad protein. This causes proteolysis, which is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion; proteases come and digest the mis-folded fragments and proteins. The problem occurs when the proteins do not dissolve in proteolysis. This happens because the misfolded proteins sometimes become robust enough that they are not dissolved by normal proteolysis. When the fragments do not dissolve they get spit out of proteolysis and they aggregate to form oligomers. The reason they aggregate is that the parts of the protein that do not dissolve in proteolysis are the -pleated sheets, which are extremely hydrophobic. They are usually sequestered in the middle of the protein, while parts of the protein that are more soluble are found near the outside. When they are exposed to water, these hydrophobic pieces tend to to aggregate with other hydrophobic pieces. This ball of fragments gets stabilized by GAG's (glycosaminoglycans) and SAP (serum amyloid P- a component found in amyloid aggregations that is thought to stabilize them and prevent proteolytic cleavage). These stabilized balls of protein fragments are called oligomers . The oligomers can aggregate together and further stabilize to make amyloid fibrils. Both the oligomers and amyloid fibrils can cause cell toxicity and organ dysfunction. [5]

Classification
The names of the amyloid usually start with the letter "A". Following is a brief description of the more common types of amyloid: Official abb. AL AA A Amyloid type/Gene OMIM

Description AL amyloidosis / multiple myeloma. Contains immunoglobulin light-chains (,) derived from plasma cells. AA amyloidosis Found in Alzheimer disease brain lesions.

amyloid light chain SAA amyloid/APP

254500

605714

ATTR

transthyretin

A mutant form of a normal serum protein that is deposited in the genetically determined familial amyloid 105210 polyneuropathies. TTR is also deposited in the heart in senile systemic amyloidosis.[6] Also found in Leptomeningeal amyloidosis.

A 2 M AIAPP

2 microglobulin amylin

Not to be confused with A, 2 m is a normal serum protein, part of major histocompatibility complex (MHC) Class 1 molecules. Haemodialysis-associated amyloidosis Found in the pancreas of patients with type 2 diabetes. In prion diseases, misfolded prion proteins deposit in tissues and resemble amyloid proteins. Some examples are CreutzfeldtJakob disease (humans), BSE or "mad cow disease" (cattle), and scrapie (sheep and goats). Finnish type amyloidosis Cerebral amyloid angiopathy, Icelandic-type Familial visceral amyloidosis Familial visceral amyloidosis Familial visceral amyloidosis Primary cutaneous amyloidosis Cerebral amyloid angiopathy, British-type

APrP

prion protein

123400

AGel ACys AFib ALys ? ABri

GSN CST3

105120 105150 105200 105200 105200 105250 176500

AApoA1 APOA1 FGA LYZ OSMR ITM2B

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Amyloidosis - Wikipedia, the free encyclopedia

ADan APro AKer AANF ACal prolactin

Danish-type Prolactinoma

117300

keratoepithelin Familial corneal amyloidosis atrial natriuretic factor calcitonin Senile amyloid of atria of heart Medullary carcinoma of the thyroid

As of 2010, there were 27 human and nine animal fibril proteins classified, along with eight inclusion bodies.[7]

Symptoms
There are numerous symptoms that are associated with this disease. The most common ones have to do with the heart, such as heart failure, arrhythmia, and an irregular heart beat. Also the respiratory tract can be affected and cause hemoptysis. Usually the spleen enlarges and sometimes ruptures. The gastrointestinal tract is usually affected and causes vomiting, hemorrhaging and diarrhea. The amyloidosis can also affect the motor functions and cause polyneuropathy. When the amyloid fibrils and oligomers get to the skin they can cause skin lesions and petechiae. One of the most famous symptoms is macroglossia.[5]

Diagnosis
The major way that this disease is discovered is through a biopsy of the kidney, gastrointestinal tract or the salivary glands. Once medical professionals have this biopsy, they stain it with a variety of different stains. The most common stain is the Congo Red Dye Test. In this test the normal skin and tissue turns a light red color but the amyloid tissue turns a dark red. Under polarized light the amyloid proteins glow green with this red dye test. Also, they can test it with Thioflavin T, which makes the amyloid fibrils glow in the dark and they need a specific microscope to see this type of stain. The problem with these stains is that they only show that a person has amyloidosis, not what type of amyloidosis. To find out the certain types of amyloidosis, they need to go through more stains, such as the potassium permanganate stain which shows up in the AA but not the AL (The AA and Al versions are the most similar forms of this disease). Other than biopsy, one can look at a urine or blood sample. If the sample has protein in it then the doctors can determine what type of protein it is and if it is amyloid or not. They do this through immunofixation and nephelometry.[5]

Alternative classifications
An older, clinical, method of classification refers to the amyloidoses as systemic or localised Systemic amyloidoses affect more than one body organ or system. Examples are: AL, AA and A2m.[8] Localised amyloidoses affect only one body organ or tissue type. Examples are: A, IAPP, Atrial natriuretic factor (in isolated atrial amyloidosis) and Calcitonin (in medullary carcinoma of the thyroid) [8] Another classification is primary or secondary. Primary amyloidoses arise from a disease with disordered immune cell function such as multiple myeloma and other immunocyte dyscrasias. Secondary (reactive) amyloidoses are those occurring as a complication of some other chronic inflammatory or tissue destructive disease. Examples are reactive systemic amyloidosis.[8]

Additional images
http://en.wikipedia.org/wiki/Amyloidosis[2/27/2011 7:48:51 AM]

Amyloidosis - Wikipedia, the free encyclopedia

Small bowel duodenum with amyloid deposition congo red 10X

Amyloidosis, dystrophic calcification

Small bowel duodenum with amyloid deposition 20X

Amyloidosis, Node, Congo Red

Amyloidosis, blood vessels, H&E

Amyloidosis, lymph node, H&E

Amyloidosis, lymph node, polarizer

Cardiac amyloidosis[disambiguation nee . H&E stain.

References
1. ^ "Atlas of Pathology" . 2. ^ Pavelka, Margit; Roth, Jrgen. Functional Ultrastructure: An Atlas of Tissue Biology and Pathology. Springer. pp. 258. ISBN 3-21183564-4. 3. ^ Mok KH, Pettersson J, Orrenius S, Svanborg C (March 2007). "HAMLET, protein folding, and tumor cell death". Biochem. Biophys. Res. Commun. 354 (1): 17. doi:10.1016/j.bbrc.2006.12.167 . PMID 17223074 . 4. ^ Pettersson-Kastberg J, Aits S, Gustafsson L, et al. (November 2008). "Can misfolded proteins be beneficial? The HAMLET case". Ann. Med. 41 (3): 115. doi:10.1080/07853890802502614 . PMID 18985467 .
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6. ^ Hassan W, Al-Sergani H, Mourad W, Tabbaa R (2005). "Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management" . Tex Heart Inst J 32 (2): 17884. PMID 16107109 . 7. ^ Sipe JD, Benson MD, Buxbaum JN, et al. (September 2010). "Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis" . Amyloid 17 (3-4): 101104. doi:10.3109/13506129.2010.526812 . PMID 21039326 . 8. ^ a b c Table 5-12 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology

http://en.wikipedia.org/wiki/Amyloidosis[2/27/2011 7:48:51 AM]

Amyloidosis - Wikipedia, the free encyclopedia 5. ^ [1] , Karp, Judith E., ed. Amyloidosis Diagnosis and Treatment. Rochester: Humana, 2010. Online Source. . . Philadelphia: Saunders. ISBN 14160-2973-7. 8th edition.

External links
Amyloidosis
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at the Open Directory Project

Metabolic disease: amyloidosis (E85, 277.3)
AA ATTR A2M AL A/APP AIAPP ACal APro AANF ACys ABri AL amyloidosis AA amyloidosis Systemic amyloidosis A2M/Haemodialysis-associated amyloidosis AGel/Finnish type amyloidosis AA/Familial Mediterranean fever ATTR/Transthyretin-related hereditary amyloidosis Heart Brain Kidney AANF/Isolated atrial amyloidosis Familial amyloid neuropathy ACys+ABri/Cerebral amyloid angiopathy A/Alzheimer's disease AApoA1+AFib+ALys/Familial renal amyloidosis Primary cutaneous amyloidosis Amyloid purpura Thyroid: ACal/Medullary thyroid cancer Endocrine Pituitary: APro/Prolactinoma Pancreas: AIAPP/Insulinoma AIAPP/Diabetes mellitus type 2

Common amyloid forming proteins

Organ-limited amyloidosis

Cutaneous

Categories: Diseases and disorders | Skin conditions resulting from errors in metabolism | Protein folding

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