Disease Directory Transthyretin Amyloidosis
Cardiovascular

Transthyretin Amyloidosis

Also known as: ATTR amyloidosis, hATTR, familial amyloid polyneuropathy, TTR amyloidosis

Prevalence

Wild-type: estimated 1–5 per 10,000 over age 65; hereditary: varies by variant

Onset

Adulthood; hereditary form typically 30–60; wild-type after 60

Type

Autosomal dominant (hereditary); acquired (wild-type)

Gene

TTR

About Transthyretin Amyloidosis

Transthyretin Amyloidosis is caused by misfolding and extracellular deposition of amyloid fibrils derived from transthyretin, a liver-produced transport protein, in multiple organs including the heart, peripheral nerves, and carpal tunnel. Hereditary ATTR (hATTR), caused by autosomal dominant TTR mutations such as Val30Met and Val122Ile, presents with polyneuropathy and/or cardiomyopathy depending on the variant, while wild-type ATTR (ATTRwt) causes cardiomyopathy exclusively and is substantially underdiagnosed in elderly men with heart failure with preserved ejection fraction. Disease-modifying therapies including TTR stabilisers (tafamidis) and RNA-silencing agents (patisiran, vutrisiran) have transformed the management landscape.

Common Clinical Features

Cardiac restrictive physiology with heart failure symptoms Peripheral sensorimotor neuropathy (in hATTR) Autonomic neuropathy (orthostatic hypotension, GI dysmotility) Carpal tunnel syndrome, often bilateral and preceding diagnosis by years Lumbar spinal stenosis Increased left ventricular wall thickness with preserved or reduced EF Discordant low-voltage ECG relative to echocardiographic wall thickness Increased myocardial uptake on technetium pyrophosphate bone scan

Clinical Trial Eligibility Tips

What to know before applying to Transthyretin Amyloidosis trials.

Tissue biopsy with amyloid typing (Congo red staining and immunohistochemistry or mass spectrometry) or positive bone scan with genetic TTR testing is required to confirm ATTR vs. AL amyloidosis, a critical distinction for trial eligibility.

Current or prior use of tafamidis or RNA-silencing therapy may influence eligibility for interventional trials; a detailed treatment history with dates is essential.

Functional capacity (6-minute walk test distance and NYHA class) and biomarkers (NT-proBNP, troponin) are standard inclusion and stratification criteria; recent results should be available.

Patient Resources

Patient Organization

Amyloidosis Research Consortium

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Natural History Registry

Transthyretin Amyloidosis Outcomes Survey (THAOS)

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Orphanet

European reference resource for rare diseases (ORPHA:85451)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting Transthyretin Amyloidosis trials

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