Summary about Disease
Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive systemic disease characterized by the misfolding and aggregation of normal (wild-type) transthyretin (TTR) protein. These misfolded TTR proteins form amyloid fibrils that deposit in various tissues and organs, primarily the heart, but also the peripheral nerves, carpal tunnel, and other organs. This deposition leads to organ dysfunction and ultimately, heart failure and/or nerve damage.
Symptoms
Symptoms vary depending on the organs affected, but common signs include:
Heart: Shortness of breath, fatigue, swelling in the legs and ankles (edema), palpitations, abnormal heart rhythms (arrhythmias), lightheadedness or fainting.
Nerves: Numbness, tingling, or pain in the hands and feet (peripheral neuropathy), carpal tunnel syndrome, weakness, diarrhea, constipation, orthostatic hypotension (dizziness upon standing).
Other: Carpal tunnel syndrome (often preceding other symptoms by years), biceps tendon rupture, lumbar spinal stenosis.
Causes
ATTRwt amyloidosis is caused by the age-related instability of the normal transthyretin (TTR) protein. As individuals age, the TTR protein becomes more prone to misfolding and forming amyloid fibrils. The precise reasons for this age-related instability are not fully understood, but it is believed to be a combination of genetic predisposition and environmental factors. It is not caused by a genetic mutation like hereditary ATTR amyloidosis (ATTRv).
Medicine Used
Tafamidis: A TTR stabilizer that binds to TTR and prevents it from misfolding and forming amyloid fibrils.
Diflunisal: (Less commonly used due to side effects) Another TTR stabilizer, but non-selective COX inhibitor.
Heart Failure Medications: Diuretics, ACE inhibitors, beta-blockers, and other medications may be used to manage heart failure symptoms.
Pain Medications: Medications may be used to manage pain associated with peripheral neuropathy or carpal tunnel syndrome.
Inotersen and Patisiran: These are RNA interference therapeutics to reduce the production of TTR; however, are not specifically approved for ATTRwt, but instead ATTRv.
Is Communicable
No. ATTRwt amyloidosis is not a communicable disease. It is not caused by an infectious agent and cannot be transmitted from person to person.
Precautions
There are no specific precautions to prevent ATTRwt amyloidosis, as it is primarily an age-related condition. However, maintaining a healthy lifestyle, including regular exercise and a balanced diet, may promote overall cardiovascular health. Early diagnosis and treatment are crucial to slowing the progression of the disease.
How long does an outbreak last?
ATTRwt amyloidosis is not an "outbreak" disease like an infection. It is a chronic, progressive condition that develops over time. The duration of the disease varies significantly from person to person, but without treatment, it typically leads to significant morbidity and mortality within a few years of diagnosis.
How is it diagnosed?
Diagnosis typically involves a combination of the following:
Clinical evaluation: Assessment of symptoms and medical history.
Echocardiogram: To evaluate heart structure and function.
Electrocardiogram (ECG): To assess heart rhythm.
Blood tests: Including TTR levels and cardiac biomarkers (e.g., BNP, troponin).
Bone Scan with DPD: Looking for cardiac uptake.
Cardiac MRI: To assess for amyloid infiltration in the heart.
Tissue biopsy: A biopsy of affected tissue (e.g., heart, fat pad) followed by staining for amyloid deposits (e.g., Congo red staining) and immunohistochemistry or mass spectrometry to identify the type of amyloid protein.
Genetic Testing: To rule out hereditary ATTR amyloidosis (ATTRv). This is important, even though the initial suspicion is ATTRwt.
Timeline of Symptoms
The timeline of symptoms can vary widely, but a general progression is often seen:
Early: Carpal tunnel syndrome (often years before other symptoms), biceps tendon rupture.
Initial: Mild shortness of breath, fatigue, and/or peripheral neuropathy.
Progressive: Worsening heart failure symptoms (e.g., increasing shortness of breath, edema), more severe peripheral neuropathy (e.g., pain, weakness, numbness), and development of other organ involvement.
Advanced: Severe heart failure, significant disability due to neuropathy, and ultimately, death.
Important Considerations
ATTRwt amyloidosis is often underdiagnosed, as its symptoms can mimic other conditions, such as heart failure due to other causes.
Early diagnosis and treatment are crucial to slowing the progression of the disease and improving outcomes.
A multidisciplinary approach involving cardiologists, neurologists, and other specialists is essential for managing ATTRwt amyloidosis.
Clinical trials are ongoing to investigate new treatments for ATTRwt amyloidosis.
Patients and their families should receive genetic counseling to rule out the possibility of hereditary ATTR amyloidosis (ATTRv) and to understand the implications for other family members.