Abstract
Objectives Hereditary Transthyretin amyloidosis (ATTRv) is characterised by progressive sensorimotor and autonomic neuropathy, and cardiac failure. We aim to describe the spectrum of ATTRv neuropathy in Australia.
Methods A retrospective analysis of ATTRv patients attending Australian Amyloidosis Network clinics between 2007–2022 was performed. TTR variants, clinical features and treatments were evaluated.
Results 161 individuals were identified (62% NSW/ACT, 20% QLD, 12% VIC/TAS, 4% WA, 2% SA). Average age was 59.4 years (range 21.5–91.4). 53% were male. 37% were presymptomatic (average age 52.7 years, range 21.5–71.0). 24 genetic variants were identified, including Thr60Ala (31%), Val30Met (23%), Val122Ile (12%), Ala97Ser (6%), Glu89Gln (5%).
The diagnosis rate has increased from 2 p.a in 2011–13 to 5 p.a in 2015–17, and 12 p.a in 2020–22. The average time to diagnosis was 3.8 years (range 1–15). 13 asymptomatic individuals developed symptomatic disease over an average 2.3 years (range 0–8).
40% had neuropathic-predominant disease, 32% cardiac, 25% mixed cardiac and neuropathic, and 3% had other organ-predominant disease. Of the 130 living individuals 45% had a PND score of 0, 22% PND1,10% PND2, and 9% PND3a or above. Similarly, 53% of individuals had a FAP0, 31% FAP1, 15% FAP2 and 1% FAP3.
Of individuals with PND0–2, only 22% were on highly efficacious treatments, all via clinical trial or compassionate access scheme.
Conclusions Our study is the first to demonstrate the spectrum of ATTRv in Australia. Affordable TTR genotyping and access to highly efficacious novel therapies remain substantial unmet needs in this population.
