Understanding the debilitating nature of the disease
SYSTEMIC
ATTR amyloidosis is characterised by the deposition of transthyretin (TTR) amyloid fibrils in various organs and tissues resulting in multisystem dysfunction1,3–6
PROGRESSIVE
Disease progression is associated with significant disability and poor quality of life7–13
POTENTIALLY FATAL
The disease is marked by substantial morbidity and has a poor prognosis.14–17
For heart failure patients with ATTR amyloidosis, median survival can be as short as 2.6 years18
ATTR amyloidosis is a protein-misfolding disease of the transthyretin (TTR) protein1
The source of the disease is TTR which is produced primarily in the liver3,19
Liver
(where 90% of TTR is produced)
Transthyretin
tetramer destabilises
tetramer destabilises
Tetramer dissociates into monomers
Monomers misfold
and aggregate into amyloid fibrils
and aggregate into amyloid fibrils
Amyloid deposits throughout the body
Watch this video to learn more about the disease mechanism of ATTR amyloidosis
The disease is classified as hereditary or wild type19
Hereditary ATTR (ATTRv):
Instability of TTR is due to mutations in the TTR gene1,19
Wild-type ATTR (ATTRwt):
Instability of TTR may be due to unknown environmental and age-related factors19
UNDERSTAND MORE ABOUT THE DIFFERENCES BETWEEN HEREDITARY AND WILD-TYPE
- Age of onset is typically >30 years20
- Symptoms manifest as cardiomyopathy (CM), polyneuropathy (PN) or both1
- Patients are typically aged >60 years and male21
- Symptoms generally manifest as CM1
Mutations associated with ATTRv amyloidosis
- The most common TTR mutations in the UK and Ireland are T80A, V142I and V50M22
- The V142I mutation is predominantly linked to cardiac manifestations; autonomic dysfunction and peripheral neuropathy are clinically rare8,21–23
- The T80A mutation typically exhibits a mixed clinical phenotype, encompassing both cardiac and neuropathic features21,22
- It has been shown that around 1 in 1000 people in the UK carry likely pathogenic TTR variants, surpassing known prevalence rates24
- In the UK, there are thought to be around 600 people with wild-type ATTR-CM and 200 people with hereditary ATTR-CM25
- The true prevalence of ATTR-CM in the UK is likely underestimated due to potential under-diagnosis and under-reporting of the condition25
Patients are often defined by CM or PN presentation. In the UK, up to 29% of patients with ATTRv and up to 8% with ATTRwt have mixed presentation26
Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is defined as patients presenting with manifestations that predominantly affect the heart1,27
Transthyretin amyloidosis with polyneuropathy (ATTR-PN) is defined as patients presenting with manifestations that predominantly affect the peripheral nerves19
It is important to suspect ATTR amyloidosis signs and symptoms to facilitate earlier diagnosis and treatment1
Timely diagnosis and treatment of ATTR amyloidosis may help to improve patient outcomes28
Get in touch
If you have any questions about ATTR amyloidosis in the United Kingdom or would like to speak to an AstraZeneca medical representative, please contact us
GB-62816 I April 2025
