“Donegal Amy” is a nickname for hereditary transthyretin amyloidosis with the Thr60Ala mutation. It usually has a mixed phenotype, meaning patients have symptoms of both transthyretin amyloid cardiomyopathy (ATTR-CM) and transthyretin amyloid polyneuropathy (ATTR-PN), the form of ATTR that affects the nerves.
“Donegal Amy” is found mainly in families with roots in the northwest coast of Donegal, Ireland.
What causes Donegal Amy?
The story of Donegal Amy began thousands of years ago, during the time of an Irish king named Conall Gulban, who ruled the area that is now Donegal. At some point in his family line, a small change happened in the gene transthyretin. This change was passed down through the generations.
While worldwide this condition is rare, it’s more common in Donegal. Researchers believe that about one in 100 people in Donegal may have this gene change. As people from Donegal moved to other countries over the centuries, they unknowingly brought the genetic condition with them.
Read more about ATTR-CM causes and risk factors
What does the Thr60Ala gene mutation do?
Donegal Amy is caused by a small glitch in the transthyretin gene. Transthyretin (or TTR for short) is a protein made by the liver that normally helps carry vitamin A and thyroid hormone. But in people with a faulty TTR gene, the protein doesn’t fold the right way. It clumps together to form amyloid fibrils, which build up in the body, especially in the heart and nervous system. This buildup can lead to serious health problems over time.
What are the symptoms?
Donegal Amy usually appears between the ages of 45 and 80, most often after age 60. Men are slightly more likely to be affected than women.
The disease can affect both the heart and the nerves. One of the earliest signs — seen in nearly half of patients — is carpal tunnel syndrome, which causes tingling, numbness or weakness in the hands.
Other common symptoms include:
- Fatigue (feeling very tired).
- Unexplained weight loss.
- Swelling in the legs and feet.
- Shortness of breath.
- Problems with bowel or bladder control.
- Difficulty walking.
As the condition progresses, it causes heart and nerve-related complications.
Are there any treatments?
As with other forms of ATTR-CM, for a long time there wasn’t much that could be done. But now, there are new medicines that help stop the faulty TTR protein from forming and causing damage. Two of the main ones used by patients with Donegal Amy are called patisiran and inotersen. They don’t cure the disease, but they slow it down and improve patients’ quality of life. Both therapies are approved by the U.S. Food and Drug Administration to treat the aspect of Donegal Amy that impacts the nerves, but not the heart.
Advocacy efforts
Donegal Amy came into the spotlight when Martin McGuinness, a well-known Northern Irish politician, died of amyloidosis in 2017. His mother was from Donegal.
Amyloidosis Ireland is a volunteer group that works to raise awareness about ATTR amyloidosis and the Donegal Amy variant. The organization pushes for quicker diagnosis, better access to treatment and provides support for anyone affected by the disease.
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