What TTR Amyloid Stands For
TTR stands for Transthyretin, making "TTR amyloid" refer to Transthyretin amyloidosis—a disease caused by abnormal fibrils derived from the transthyretin protein that aggregate and deposit in tissues and organs. 1
Protein Origin and Function
- Transthyretin (TTR) is a protein produced mainly by the liver that normally functions as a transport protein in the blood 1
- In ATTR amyloidosis, this TTR protein misfolds and aggregates into amyloid fibrils that deposit in various organs, particularly the heart and peripheral nerves 1
Two Forms of ATTR Amyloidosis
ATTR amyloidosis occurs in two distinct forms:
- Hereditary (variant) ATTR (ATTRv or ATTRm): Caused by mutations in the TTR gene, transmitted in an autosomal-dominant manner with variable penetrance 1
- Acquired (wild-type) ATTR (ATTRwt): Normal "wild-type" TTR protein misfolds to form amyloid deposits, usually due to aging, formerly known as senile systemic amyloidosis 1
Clinical Manifestations
- ATTR amyloidosis commonly manifests as cardiomyopathy (ATTR-CM), which is associated with a particularly poor life expectancy of 2-6 years after diagnosis 1
- The disease can also present as familial amyloid polyneuropathy when it mainly affects the nerves, or familial amyloid cardiomyopathy when it primarily affects the heart 1
- Patients experience debilitating symptoms including exercise intolerance, fatigue, decreased functional capacity, and diminished quality of life 1
Distinction from Other Amyloidosis Types
- ATTR amyloidosis must be distinguished from AL amyloidosis, which results from abnormal immunoglobulin light chains produced by bone marrow plasma cells 1, 2
- TTR gene sequencing is critical to differentiate hereditary variant (ATTRv) from wild-type (ATTRwt) disease and to determine eligibility for specific therapies 3