Amyloidosis is a heterogeneous group of diseases characterized by tissue infiltration with misfolded protein precursors.
The term amyloid is used to describe a substance with a homogeneous eosinophilic appearance by light microscopy, a green birefringence on polarizing light microscopy, and a characteristic β-pleated sheet appearance by x-ray diffraction.
Terms such as primary, secondary, senile, dialysis-associated, and myeloma-associated have been abandoned in favor of the etiologically based, chemical terminology (Table 71–1) (eg, immunoglobulin light chain amyloidosis is termed AL amyloidosis).
TABLE 71–1NOMENCLATURE OF AMYLOIDOSIS |Favorite Table|Download (.pdf) TABLE 71–1NOMENCLATURE OF AMYLOIDOSIS
|Amyloid Type ||Subunit Protein ||Clinical Organ Involvement |
|AL (κ or λ) or AH || |
Immunoglobulin light or heavy chain
May be localized or systemic
|AA ||Secondary serum amyloid A || |
|ATTR (age related) ||Senile systemic transthyretin || |
|ATTR (mutant) ||Familial transthyretin || |
|A Lect-2 || |
Leukocyte chemotactic factor
No mutation found
|A Ins ||Insulin localized to injection sites ||Skin |
|A Fib ||Fibrinogen A-2 mutation ||Kidney |
|A β2M || |
The incidence of AL amyloidosis is rare, with an incidence of 8 per million persons per year and a median age at diagnosis of 67 years.
Amyloid A (AA) amyloidosis is increasingly rare, occurring in less than 1% of persons with chronic inflammatory diseases in the United States and Europe.
AA amyloidosis is more common in Turkey and the Middle East, where it occurs in association with familial Mediterranean fever.
AA is the only type of amyloidosis that occurs in children.
Amyloid β2-microglobulin (Aβ2M) amyloidosis usually manifests as deposits in the joint synovial and occurs in patients on long-term dialysis. The incidence is declining with changes in dialysis techniques.
The inherited amyloidoses are rare in the United States, with an estimated incidence of less than approximately 1 per 100,000 persons.
Amyloidogenic transthyretin (ATTR) amyloidosis is the most common form of familial amyloidosis and is associated with mutations of the gene encoding transthyretin (TTR).
ETIOLOGY AND PATHOGENESIS
The exact mechanism of fibril formation is unknown and may be different among the various types of amyloid.
Amyloid precursor proteins typically consist of long fibrils composed of relatively small precursor proteins with molecular weights between 4000 and 25,000 daltons.
Each amyloid fibril protein has a precursor molecule in the serum.
— The secondary structures of many of the proteins have substantial β-pleated sheet structure. The known exceptions include serum amyloid A (SAA) and cellular prion protein (PrPc), which contain little or no β folding in the precursor protein despite extensive β-sheet in the deposited fibrils.
Amyloid formation involves:
— Stimulus-generated change in the serum concentration or primary structure of amyloid precursor proteins.
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