ATTRv Definition
ATTRv stands for variant transthyretin amyloidosis (also called hereditary transthyretin amyloidosis), which is the hereditary form of ATTR amyloidosis caused by pathogenic mutations in the TTR (transthyretin) gene. 1
Key Components of the Acronym
- ATTR = Amyloid Transthyretin (referring to amyloid deposits made up of the TTR protein) 1
- v = variant (indicating the presence of a genetic mutation creating abnormal, "variant" TTR protein) 1
Distinguishing ATTRv from ATTRwt
ATTRv is fundamentally different from ATTRwt (wild-type transthyretin amyloidosis) because it involves a heritable genetic mutation in the TTR gene that produces abnormal, amyloidogenic variant TTR protein. 1
ATTRv (hereditary): Caused by TTR gene mutations that are inherited in an autosomal dominant pattern, resulting in production of destabilized mutant TTR protein that misfolds and deposits as amyloid 1, 2
ATTRwt (wild-type): Normal "wild-type" TTR protein misfolds to form amyloid deposits, usually due to aging, with no genetic mutation present 1
Clinical Manifestations
ATTRv can manifest as two primary phenotypes depending on which organ system is predominantly affected: 1
- Familial amyloid polyneuropathy (FAP): When disease mainly affects the peripheral and autonomic nervous system 1, 2, 3
- Familial amyloid cardiomyopathy: When disease mainly affects the heart 1
Diagnostic Importance
Genetic testing with TTR gene sequencing is mandatory once ATTR-CM is diagnosed to differentiate ATTRv from ATTRwt, as this distinction has critical treatment and family screening implications. 1
- TTR silencing therapies (patisiran, inotersen, vutrisiran) are only approved and effective for ATTRv polyneuropathy, not for ATTRwt disease 1, 4, 5
- Confirmation of ATTRv triggers cascade genetic testing for at-risk family members 1
- Tafamidis is approved for both ATTRv and ATTRwt cardiac amyloidosis 4, 5