II. Epidemiology
- Overall Prevalence: <200,000 in U.S. affected
III. Pathophysiology
- Disturbed endogenous Protein Metabolism
- Primary
- Secondary to chronic tissue breakdown
- Organ dysfunction arises from extracellular amyloid deposition is soft tissue and organs
IV. Types
- Many classification systems have been used (e.g. systemic, hereditary, localized)
- Modern classification is specific to the chemical analysis of the deposited Protein
- Common Types
- Amyloidosis Immunoglobulin Light Chain Fragment (AL, immunocyte dyscrasia, primary Amyloidosis)
- Incidence: 1 per 100,000 (1000 to 3000 new cases/year in U.S.)
- Small plasma cell clones produce misfolded monoclonal light chain Immunoglobulin fragments that deposit in tissues
- May be associated with Multiple Myeloma and other plasma cell dyscrasias
- Broad Protein deposition in the heart, Kidneys, liver and Gastrointestinal Tract
- Also deposits in the Peripheral Nervous System and Autonomic Nervous System
- Amyloidosis A Protein (AA, reactive Amyloidosis, secondary Amyloidosis)
- Reactive Amyloidosis to chronic inflammatory disease (e.g. Rheumatoid Arthritis, chronic infections)
- Associated with serum amyloid A deposition in jidneys, Gastrointestinal Tract and heart
- Amyloid Transport Protein Transthyretin (ATTR, senile systemic Amyloidosis)
- Less common Amyloidosis type (represents 10-20% of cases at tertiary centers)
- Associated with Alzheimer Disease, Neuropathy as well as heart deposition
- Dialysis-Related Amyloidosis (beta2M type)
- Associated with high serum concentrations of Protein precursors (beta2M)
- Associated with amyloid deposition in osteoarticular tissue, Gastrointestinal Tract and circulatory system
- Amyloidosis Immunoglobulin Light Chain Fragment (AL, immunocyte dyscrasia, primary Amyloidosis)
- Hereditary Amyloidosis
- Familial Mediterranean Fever
- Familial Amyloidotic Neuropathy
- Apolipoprotein 1 (AApoA1)
- Amyloid deposition in the heart, Kidneys, liver, Peripheral Nervous System and skin
- Mutant Fibrinogen A alpha (AFib)
- Amyloid deposition in Kidneys and liver
- Lysozyme (ALys)
- Amyloid deposition in Kidneys and liver
- Endocrine Amyloidosis
- Thyroid
- Associated with the Calcitonin precursor Protein, and the A Cal fibril Protein
- Associated with development of Medullary carcinoma
- Islets of Langerhans
- Associated with the islet amyloid precursor Protein, and the AIAPP fibril Protein
- Associated with Type 2 Diabetes Mellitus
- Thyroid
- Other Localized Amyloidosis
- Finnish-type (AGel, Gelsolin)
- Amyloid deposition in the Cornea resulting in Corneal lattice dystrophy and Corneal Neuropathy
- Finnish-type (AGel, Gelsolin)
V. Symptoms
- Asthenia
- Weight loss
- Paresthesias
- Organ specific symptoms (depending on amyloid deposition sites)
VI. Signs: Organ Specific
- Macroglossia
- Hypertension
- Lymphadenopathy
- Hepatomegaly
- Splenomegaly
- Purpura
- Nephrotic Syndrome
- Edema
- Joint Pain, Muscle pain
- Serous cavity fluid
VII. Labs
- Tissue Biopsy under Congo red or thioflavine-T staining
- Plasma cell clone analysis
- Serum and urine electrophoresis (SPEP and UPEP) with immnofixation and free light chains
- Serum Immunoglobulins altered
- Immunofluorescence in situ hybridization (FISH)
- Skeletal Survey
- Serum and urine electrophoresis (SPEP and UPEP) with immnofixation and free light chains
-
Gene Sequencing
- Hereditary Amyloidosis
VIII. Resources
- Bustamante (2023) Amyloidosis, StatPearls, Treasure Island, FL, accessed 4/22/2023
IX. References
- Baloor and Nayak (2018) Exam Preparatory Manual for Undergraduate Medicine, Jaypee Brothers Medical Publication
- Baker (2012) Methodist Debakey Cardiovasc J +PMID: 23227278 [PubMed]