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Amyloidosis
Classification & external resources

Small bowel duodenum with amyloid deposition congo red 10X
ICD-10	E85.
ICD-9	277.3
DiseasesDB	633
eMedicine	med/3377  med/3888
MeSH	D000686

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.

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, secondary 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).

Contents 1 Diagnosis 2 Systemic amyloidosis 2.1 Primary/Hereditary amyloidosis 2.2 Secondary amyloidosis 2.3 Organ-specific amyloidosis 3 Famous People who have contracted Amyloidosis 4 References 5 External links

Amyloid can be diagnosed on histological 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 or 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.

These rare hereditary disorders are usually due to point mutations in precursor proteins, and are also usually autosomal dominantly transmitted.The precursor proteins are;

• transthyretin - the most commonly implicated protein.
• lysozyme
• apolipoprotein B
• fibrinogen
• apolipoprotein A1
• gelsolin

These are far more common than the primary amyloidoses.

• AL amyloidosis (immunoglobulin light chains are the precursor protein, overproduced in multiple myeloma). This is sometimes, confusingly and erroneously, called 'primary amyloidosis'.
• AA amyloidosis (the precursor protein is serum amyloid A protein (SAA), an acute-phase protein due to chronic inflammation). In contrast to AL amyloid, this has previously been termed 'secondary amyloidosis' .These occur with a wide variety of diseases associated with chronic inflammation, such as Rheumatoid arthritis, Familial Mediterranean fever or chronic infection.
• Dialysis related amyloidosis (the precursor protein is beta-2-microglobulin which is not removed with dialysis, and thus accumulates in patients with end stage renal failure on dialysis).^[1]

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. The associated proteins are indicated in parentheses.

Neurological amyloid

• Alzheimer's disease (Aβ 39-43)
• Parkinson's disease (alpha-synuclein)
• Huntington's disease (huntingtin)
• Transmissible spongiform encephalopathies caused by prion protein (PrP) were sometimes classed as amyloidoses, as one of the four pathological features in diseased tissue is the presence of amyloid plaques. These diseases include;
  • Creutzfeldt-Jakob disease (PrP in cerebrum)
  • Kuru (diffuse PrP deposits in brain)
  • Fatal Familial Insomnia (PrP in thalamus)
  • Bovine spongiform encephalopathy (PrP in cerebrum of cows)

Cardiovascular amyloid

• Cardiac amyloidosis
  • Senile cardiac amyloidosis-may cause heart failure
• Congophilic angiopathy

Other

• Amylin deposition can occur in the pancreas in some cases of type 2 diabetes mellitus

• James Oliver Rigney, Jr. (aka. Robert Jordan)
• David Lange

1. ^ Uremia, Timothy W. Meyer and Thomas H. Hostetter, N Engl J Med, 2007 Sep 27, 357(16):1316

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

v • d • e Metabolic pathology / Inborn error of metabolism (E70-90, 270-279)
Amino acid	Aromatic (Phenylketonuria, Alkaptonuria, Ochronosis, Tyrosinemia, Albinism, Histidinemia) - Branched chain (Maple syrup urine disease, Propionic acidemia, Methylmalonic acidemia, Isovaleric acidemia, 3-Methylcrotonyl-CoA carboxylase deficiency) - Transport (Cystinuria, Cystinosis, Hartnup disease, Fanconi syndrome, Oculocerebrorenal syndrome) - Sulfur (Homocystinuria, Cystathioninuria) - Urea cycle disorder (N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthetase I deficiency, Ornithine transcarbamylase deficiency, Citrullinemia, Argininosuccinic aciduria, Hyperammonemia) - Glutaric acidemia type 1 - Sarcosinemia
Carbohydrate	Lactose intolerance - Glycogen storage disease (type I, type II, type III, type IV, type V, type VI, type VII) - fructose metabolism (Fructose intolerance, Fructose bisphosphatase deficiency, Essential fructosuria) - galactose metabolism (Galactosemia, Galactose-1-phosphate uridylyltransferase galactosemia, Galactokinase deficiency) - other intestinal carbohydrate absorption (Glucose-galactose malabsorption, Sucrose intolerance) - pyruvate metabolism and gluconeogenesis (PCD, PDHA) - Pentosuria - Renal glycosuria
Lipid storage	Sphingolipidoses/Gangliosidoses: GM2 gangliosidoses (Sandhoff disease, Tay-Sachs disease) - GM1 gangliosidoses - Mucolipidosis type IV - Gaucher's disease - Niemann-Pick disease - Farber disease - Fabry's disease - Metachromatic leukodystrophy - Krabbe disease Neuronal ceroid lipofuscinosis (Batten disease) - Cerebrotendineous xanthomatosis - Cholesteryl ester storage disease (Wolman disease)
Other lipid	Lipoprotein/lipidemias: Hyperlipidemia - Hypercholesterolemia - Familial hypercholesterolemia - Xanthoma - Combined hyperlipidemia - Lecithin cholesterol acyltransferase deficiency - Tangier disease - Abetalipoproteinemia Fatty acid: Adrenoleukodystrophy - Carnitine (Primary, I, II)
Mineral	Cu Wilson's disease/Menkes disease - Fe Haemochromatosis - Zn Acrodermatitis enteropathica - PO43− Hypophosphatemia/Hypophosphatasia - Mg2+ Hypermagnesemia/Hypomagnesemia - Ca2+ Hypercalcaemia/Hypocalcaemia/Disorders of calcium metabolism
Fluid, electrolyte and acid-base balance	Electrolyte disturbance - Na+ Hypernatremia/Hyponatremia - Acidosis (Metabolic, Respiratory, Lactic) - Alkalosis (Metabolic, Respiratory) - Mixed disorder of acid-base balance - H2O Dehydration/Hypervolemia - K+ Hypokalemia/Hyperkalemia - Cl− Hyperchloremia/Hypochloremia
Purine and pyrimidine	Hyperuricemia - Lesch-Nyhan syndrome - Xanthinuria
Porphyrin	Acute intermittent, Gunther's, Cutanea tarda, Erythropoietic, Hepatoerythropoietic, Hereditary copro-, Variegate
Bilirubin	Unconjugated (Gilbert's syndrome, Crigler-Najjar syndrome) - Conjugated (Dubin-Johnson syndrome, Rotor syndrome)
Glycosaminoglycan	Mucopolysaccharidosis - 1:Hurler/Hunter - 3:Sanfilippo - 4:Morquio - 6:Maroteaux-Lamy - 7:Sly
Glycoprotein	Mucolipidosis - I-cell disease - Pseudo-Hurler polydystrophy - Aspartylglucosaminuria - Fucosidosis - Alpha-mannosidosis - Sialidosis
Other	Alpha 1-antitrypsin deficiency - Cystic fibrosis - Amyloidosis (Familial Mediterranean fever) - Acatalasia