Dr Gerard Giblin
Consultant Cardiologist, Mater University Hospital
Amyloidosis is a group of disorders caused by the build-up of an abnormal protein, amyloid, in multiple organs, leading to dysfunction. The two most common forms are light chain (AL) and transthyretin (TTR) amyloidosis.
Transthyretin is produced in the liver and normally carries thyroid hormone and vitamin A. In TTR amyloidosis, the protein becomes unstable and forms amyloid fibrils. These can build up in nerves, causing neuropathy and/or the heart, making it thicker, stiffer and less efficient at pumping.
Two main types of TTR amyloidosis
The two main types are wild-type and hereditary. Wild-type TTR amyloidosis is the most common form and typically occurs in people as they age, and it is not genetic. Hereditary TTR amyloidosis results from changes in the TTR gene and tends to present earlier, often in the 50s or 60s. Ireland has a native form of hereditary TTR amyloid, T60A — sometimes called ‘Donegal Amy’ as it is more prevalent in families originally from the northwest.
What are the common symptoms?
The heart and nervous system are the most commonly involved organs. Symptoms are often subtle at first and can be mistaken for other common conditions, leading to delays in diagnosis. These include:
- Shortness of breath, especially during physical activity or when lying down;
- Swelling in the legs or abdomen
- Fatigue
- An irregular heartbeat or palpitations
- Dizziness associated with low blood pressure
- Altered bowel habit with weight loss
- Carpal tunnel syndrome
In hereditary disease, nerve involvement in the hands and feet is common, causing pain, numbness or tingling that may precede cardiac symptoms.
Early diagnosis and treatment can make
a significant difference in improving
symptoms and limiting the
progression of the condition.
How is it diagnosed?
Diagnosis involves a combination of physical examination, specialised blood tests to rule out a bone marrow problem and cardiac imaging (including an echocardiogram or cardiac MRI and a nuclear test called a DPD scan).
A small number of patients will need a biopsy to help make the diagnosis or specialised nerve testing to assess for nervous system involvement. Once the diagnosis is made, genetic testing is recommended to determine whether the hereditary form is present.
What treatments are available?
While TTR cardiac amyloid was once considered untreatable, major advances in recent years have led to treatment options that slow the progression of the disease and improve quality of life and are now available to patients in the Republic of Ireland.
Treatments include oral medication that stabilises the transthyretin protein or an injectable drug that reduces its production, preventing further amyloid build-up. Patients in Ireland now have the opportunity to take part in clinical trials of promising new treatments, including gene editing for those with the condition, as well as a treatment to delay amyloid build-up in those who carry a gene that puts them at risk.
Support and specialist clinics for amyloidosis
In cases of hereditary TTR amyloid, family members are encouraged to meet with a genetic counsellor who can advise about family screening. If you or a family member has been diagnosed or suspected of having transthyretin cardiac amyloidosis, speak with your GP or cardiologist about referral to a specialist amyloid clinic.
Early diagnosis and treatment can make a significant difference in improving symptoms and limiting the progression of the condition.
