Hereditary ATTR amyloidosis
Hereditary transthyretin amyloidosis (hATTR) is a rare, inherited condition that can affect multiple organs. It occurs when mutations in the transthyretin (TTR) gene destabilize the protein, causing it to misfold and form amyloid deposits. These deposits gradually damage tissues, leading to serious complications. Over 130 pathogenic variants have been identified, each associated with different symptoms and disease patterns.
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What are the hallmark symptoms of hATTR amyloidosis?
Symptoms of hATTR usually begin in adulthood and worsen over time, primarily affecting the neurological, cardiac, and autonomic systems.
Neurological signs may include:
- Numbness
- Tingling, shooting, or burning pain
- Muscle weakness
- Bilateral carpal tunnel syndrome
Autonomic issues often present as:
- Digestive problems
- Bladder dysfunction
- Orthostatic hypotension
Cardiac involvement can lead to:
- Heart failure
- Arrhythmias
- Shortness of breath
- Swelling
Other features include weight loss, kidney disease, eye problems such as glaucoma, and, in advanced cases, stroke-like episodes or cognitive decline. Early diagnosis is critical for better outcomes.
Which diagnostic tests are most reliable for hATTR?
Diagnosing hATTR starts with genetic testing: TTR gene sequencing remains the gold standard. Tissue biopsy with Congo red staining and protein typing confirms amyloid deposits.
Additional assessments, such as nerve conduction studies, cardiac imaging (echocardiography, magnetic resonance imaging), bone scintigraphy, and biomarker tests (NT-proBNP, troponins), help determine disease extent.
What are the current therapies for managing hATTR?
Treatment for hATTR aims to slow progression and manage organ involvement. TTR stabilizers (tafamidis, diflunisal) prevent amyloid formation, while gene-silencing drugs (patisiran, inotersen vutrisiran) reduce TTR production and improve neuropathy. Liver transplantation is now less common; emerging options include monoclonal antibodies and epigallocatechin gallate (EGCG). Early initiation of therapy is essential for improving prognosis.
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