Hereditary ATTR amyloidosis

Hereditary ATTR (transthyretin) amyloidosis is a genetic condition in which an abnormal form of the transthyretin protein misfolds and accumulates as amyloid deposits in various body tissues, most significantly affecting the heart and peripheral nerves. It typically presents in mid to later adulthood, though age of onset varies with the specific gene mutation. It is a progressive condition requiring specialist cardiology and neurology input.

It is caused by inherited mutations in the TTR gene, which codes for the transthyretin protein, causing the protein to be structurally unstable and prone to misfolding into amyloid deposits. It is inherited in an autosomal dominant pattern, meaning each child of an affected parent has a 50% chance of inheriting the mutation. Different specific mutations are associated with somewhat different patterns and severity of disease.

Symptoms depend on which organs are predominantly affected but can include progressive numbness and tingling in the limbs, muscle weakness, symptoms of heart failure such as breathlessness and fatigue, irregular heart rhythms, and sometimes digestive symptoms or carpal tunnel syndrome. Symptoms typically develop and progress gradually over years. The specific pattern of symptoms can vary considerably even within the same family, depending partly on the specific TTR mutation involved.

Yes, it is a progressive, serious condition that can significantly affect heart function and nerve health over time if untreated, though the development of newer specific treatments has meaningfully improved the outlook for many patients. Early diagnosis and treatment can help slow disease progression and improve quality of life. Ongoing specialist cardiology and neurology follow-up is important to monitor and manage disease progression.

Yes, as the name suggests, it is an inherited genetic condition, passed on in an autosomal dominant pattern. Genetic testing can confirm the diagnosis and identify the specific mutation involved, which can help predict the likely pattern of disease and guide family screening. Genetic counselling is recommended for affected families to help relatives understand their own risk and testing options.

Treatment options have expanded significantly in recent years and now include specific medications that stabilise the transthyretin protein or reduce its production, helping to slow disease progression. Supportive treatment for specific organ involvement, such as heart failure medication or management of neuropathy symptoms, is also an important part of care. A specialist multidisciplinary team, often including cardiology, neurology, and genetics, coordinates this comprehensive treatment approach.

There is currently no cure for the underlying genetic condition, but modern targeted treatments can significantly slow disease progression and, in some cases, lead to meaningful improvement in symptoms and quality of life. Earlier diagnosis and treatment generally lead to better long-term outcomes, since less amyloid damage has accumulated before treatment begins. Ongoing research continues to develop new treatment options for this condition.

Hereditary ATTR amyloidosis is caused by an inherited gene mutation and can affect younger adults, often with a strong family history, whereas wild-type ATTR amyloidosis occurs without a genetic mutation, typically in older men, and is thought to relate to age-related instability of the normal transthyretin protein. Both cause similar amyloid deposits and symptoms, particularly affecting the heart, but genetic testing distinguishes between the two, which is relevant for family screening and, in some cases, treatment choice. This distinction is an important part of the diagnostic process for anyone newly found to have ATTR amyloidosis.

See a specialist if you have unexplained progressive numbness, weakness, or symptoms of heart failure, particularly with a family history of similar symptoms or a known diagnosis of ATTR amyloidosis in a relative. A private cardiology or neurology assessment, including relevant genetic testing, can typically be arranged within about one to two weeks. Because early treatment improves outcomes, prompt referral to a specialist familiar with this condition is valuable if it is suspected.