Primary amyloidosis classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Shaghayegh Habibi, M.D.[3]

Overview

Amyloidosis may be classified on the basis of type of amyloidogenic protein and associated clinical syndromes into primary (AL) amyloidosis, secondary (AA) amyloidosis, familial (AF) amyloidosis, transthyretin (ATTRwt) amyloidosis and dialysis-associated (AH) amyloidosis. It can also be classified based on extent of organ system involvement.

Classification

Classification Based on Precursor of Amyloidogenic Protein: ^[1]^[2]

Type	Abbreviation	Amyloidogenic Protein/Fibril	Acquired/Inherited	Most Common Organ Involvement	Associated Conditions
Primary amyloidosis	AL	Light chains of immunoglobulines (most common type)	Acquired	Heart and kidneys	Monoclonal gammopathy
Secondary amyloidosis	AA	Serum amyloid A protein	Acquired	Kidneys (early), heart and liver (late)	Chronic inflammatory diseases: Rheumatoid arthritis Juvenile inflammatory arthritis Intravenous drug use Familial periodic fever syndromes
Senile systemic or wild-type amyloidosis	ATTRwt/ATTRvar	Wild-type transthyretin (TTRwt) Abnormal TTR gene (TTRvar)	Acquired (ATTRwt) or Hereditary (ATTRvar)	Heart and nerves (more common in hereditary type)	Senile restrictive cardiomyopathy/Transthyretin-related amyloidosis wild-type ATTRwt common in males and exhibits involvement of ligaments and tenosynovium ATTRvar may involve eyes and leptomeninges
β2-microglobulin-related amyloidosis	AH	ß2-microglobulin	Acquired or Hereditary	Nerves (peripheral and autonomic)	Long-term hemodialysis
Leucocyte cell–derived chemotaxin 2 related amyloidosis	ALect2	Leucocyte cell–derived chemotaxin 2	Acquired	Kidneys and liver	Nephrotic syndrome Proteinuria
Fibrinogen A alpha-chain associated amyloidosis	AF	Fibrinogen	Hereditary	Kidneys and liver	Familial polyneuropathy/cardiomyopathy/nephropathy
Abnormal Apolipoprotein A-I, AII, and AIV related amyloidosis	AApoA-I	Aberrant apolipoprotein A-I, A-II and A-IV proteins	Hereditary	Kidneys, liver and nerves (peripheral)	Testicular involvement (possible relation to steroidogenic tissues)
Lysozyme amyloid related amyloidosis	ALys	Aberrant lysozyme	Hereditary	Liver and kidneys	Gastrointestinal involvement
Gelsolin amyloid related amyloidosis	AGel	Abnormal gelsolin	Hereditary	Kidneys and nerves (peripheral and cranial)	Cranial neuropathy

Classification Based on Organ Involvement:^[3]^[4]

Classification	Subtypes	Causes	Clinical Features
Systemic amyloidosis	Primary amyloidosis (AL)	Aggregation and deposition of immunoglobulin light chains that usually produced by plasma cell clones	Nephrotic syndrome Restrictive cardiomyopathy Peripheral neuropathy Hepatomegaly with elevated liver enzymes Macroglossia Purpura and an unexplained bleeding diathesis
	Secondary amyloidosis (AA)	Chronic inflammation (TB, familial mediterranean fever, rheumatoid arthritis and multiple myeloma)	Nephrotic syndrome Heart failure
	Hereditary amyloidosis	Amyloidogenic mutations and subsequently deposition of amyloids	Heart failure Arrhythmia
Organ-specific amyloidosis	Renal amyloidosis	Immunoglobulin light-chain amyloidosis (AL amyloidosis) Transthyretin-related amyloidosis (associated with familial/mutant or senile/wild-type TTR)	Proteinuria Nephrotic syndrome Chronic renal failure
	Cardiac amyloidosis		Systolic dysfunction Diastolic dysfunction Arrhythmia
	Hepatic amyloidosis		Hepatomegaly Elevated liver enzymes
	Amyloid neuropathy		Peripheral neuropathy and autonomic neuropathy Neurodegenerative disorders: Parkinson, Alzheimer, and Huntington’s disease
	Gastrointestinal amyloidosis		Nonspecific findings: Dyspepsia, abdominal pain, diarrhea, malabsorption

Refrences

↑ Khoor A, Colby TV (February 2017). “Amyloidosis of the Lung”. Arch. Pathol. Lab. Med. 141 (2): 247–254. doi:10.5858/arpa.2016-0102-RA. PMID 28134587.
↑ Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva M, Sekijima Y, Sipe JD, Westermark P (December 2018). “Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee”. Amyloid. 25 (4): 215–219. doi:10.1080/13506129.2018.1549825. PMID 30614283. Vancouver style error: initials (help)
↑ Wechalekar AD, Gillmore JD, Hawkins PN (June 2016). “Systemic amyloidosis”. Lancet. 387 (10038): 2641–2654. doi:10.1016/S0140-6736(15)01274-X. PMID 26719234.
↑ Falk RH, Alexander KM, Liao R, Dorbala S (September 2016). “AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy”. J. Am. Coll. Cardiol. 68 (12): 1323–41. doi:10.1016/j.jacc.2016.06.053. PMID 27634125.

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[pmid28134587-1] Khoor A, Colby TV (February 2017). “Amyloidosis of the Lung”. Arch. Pathol. Lab. Med. 141 (2): 247–254. doi:10.5858/arpa.2016-0102-RA. PMID 28134587.

[pmid30614283-2] Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva M, Sekijima Y, Sipe JD, Westermark P (December 2018). “Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee”. Amyloid. 25 (4): 215–219. doi:10.1080/13506129.2018.1549825. PMID 30614283. Vancouver style error: initials (help)

[pmid26719234-3] Wechalekar AD, Gillmore JD, Hawkins PN (June 2016). “Systemic amyloidosis”. Lancet. 387 (10038): 2641–2654. doi:10.1016/S0140-6736(15)01274-X. PMID 26719234.

[pmid27634125-4] Falk RH, Alexander KM, Liao R, Dorbala S (September 2016). “AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy”. J. Am. Coll. Cardiol. 68 (12): 1323–41. doi:10.1016/j.jacc.2016.06.053. PMID 27634125.

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