Amyloidosis

Amyloidosis
Specialty	Endocrinology, cardiology, hematology

In medicine, amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues, causing disease. A protein is amyloid if, due to an alteration in its secondary structure, it takes on a particular insoluble form, called the beta-pleated sheet.

The term "amyloidosis" refers to a histological finding occurring in several different disease processes that have little in common with each other, and without additional information, the finding is of limited clinical use.

Diagnosis

Amyloid can be diagnosed on microscopic examination of affected tissue. Amyloid deposits can be identified histologically by Congo red staining and viewing under polarized light where amyloid deposits produce a distinctive 'apple green birefringence'. Further, specific tests are available to more precisely identify the amyloid protein. Biopsies are taken from affected organs (for example, the kidney), or often in the case of systemic amyloid, from the rectum, gingiva, or omentum (anterior abdominal adipose tissue).

In addition, all amyloid deposits contain serum amyloid P component (SAP), a circulating protein of the pentraxin family. Radionuclide SAP scans have been developed which can anatomically localize amyloid deposits in patients.

Bleeding under the skin, called amyloid purpura, is seen in a minority of patients with amyloidosis.

Classification of amyloid

Approximately 25 different proteins are known that can form amyloid in humans. Most of them are constituents of the plasma.

Different amyloidoses can be systemic (affecting many different organ systems) or organ-specific. Some 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).

There are at least 15 biologically distinct forms of amyloid, some more clinically significant than others. Following is a brief description of the more common types of amyloid:

Abb.	Amyloid type	Description
AL	amyloid light chain	Contains immunoglobulin light-chains (λ,κ) derived from plasma cells
AA	amyloid associated	Non-immunoglobulin protein made in the liver
Aβ	β amyloid	Found in Alzheimer disease brain lesions
ATTR	Transthyretin	A mutant form of a normal serum protein that is deposited in the genetically determined familial amyloid polyneuropathies. TTR is also deposited in the heart in senile systemic amyloidosis.
Aβ2 m	β2 microglobulin	Not to be confused with Aβ, β2m is a normal serum protein, part of major histocompatability complex (MHC) Class 1 molecules. Can occur in long term haemodialysis.
PrP	Prion related protein	In Prion diseases, misfolded prion proteins deposit in tissues and resemble amyloid proteins.

OMIM includes the following:

OMIM	Gene	Name	Number
Template:OMIM2	TTR	Senile systemic amyloidosis	(type 1)
Template:OMIM2	GSN	Finnish type amyloidosis	(type 5)
Template:OMIM2	CST3	Cerebral amyloid angiopathy, Icelandic type	(type 6)
Template:OMIM2	TTR	Leptomeningeal amyloidosis	(type 7)
Template:OMIM2	APOA1, FGA, LYZ	Familial visceral amyloidosis	(type 8)
Template:OMIM2	OSMR	Primary cutaneous amyloidosis	(type 9)
Template:OMIM2	ITM2B	Cerebral amyloid angiopathy, British type	-
Template:OMIM2, Template:OMIM2	APP	Dutch type / Italian type / Iowa type	-

Classification of amyloidosis

The amyloidoses can be classified as systemic or localised, primary or secondary, or according to which type of amyloid is deposited. By convention, a combination of these approaches are used clinically.

• Systemic amyloidoses are those which affect more than one body organ or system. Localised amyloidoses affect only one body organ or tissue type.
• 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.

• The different types of amyloid deposited (see table, above) may be either primary or secondary, systemic or localised.

Systemic amyloidosis

The common systemic amyloidoses:

Category	Amyloid type	Precursor protein	Amyloidosis
Systemic acquired	AL	Immunoglobin light chains (Bence Jones protein)	AL amyloidosis (primary amyloidosis)
Systemic hereditary	AA	SAA	AA amyloidosis (secondary amyloidosis)
Systemic hereditary	Aβ2 m	β2 microglobulin	Haemodialysis associated
Systemic hereditary	AA	SAA	Familial mediterranean fever
Systemic hereditary	ATTR	transthyretin	Familial amyloidotic polyneuropathies
Systemic hereditary	ATTR	transthyretin	Systemic senile amyloidosis

Organ-specific amyloidosis

Main article: Organ-limited amyloidosis

In almost all of the organ-specific pathologies, there is significant debate as to whether the amyloid plaques are the causal agent of the disease or instead a downstream consequence of a common idiopathic agent.

Famous People who have contracted Amyloidosis

• Robert Jordan, author of the The Wheel of Time series
• David Lange, Prime Minister of New Zealand
• Richard Caliguiri, mayor of Pittsburgh, Pennsylvania
• Louis J. Tullio, mayor of Erie, Pennsylvania
• Robert P. Casey, Governor of Pennsylvania
• Ed Guthman, Pulitzer Prize winner

Additional images

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  Amyloidosis, dystrophic calcification
• 
  Small bowel duodenum with amyloid deposition 20X
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  Amyloidosis, Node, Congo Red
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  Amyloidosis, blood vessels, H&E
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  Amyloidosis, lymph node, H&E
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  Amyloidosis, lymph node, polarizer

External links

• Overview at Mayo Clinic
• Overview at Cleveland Clinic
• [1] Boston University Amyloid Treatment and Research Program
• www.amyloidosisaustralia.org Information, support and advice to anyone with Amyloidosis