Change in prevalence of ATTR variants in Italy: Results from a national survey

Aims Hereditary transthyretin amyloidosis (ATTRv) is a rare, heterogeneous, inherited disorder caused by over 130 gene mutations. Its prevalence was estimated to 4.33/million in 2020 in Italy. Whether growing disease awareness and improved diagnostics may have increased national diagnoses in the last 4 years is unresolved. Methods and results All alive ATTRv diagnoses from 2004 to 2024 from 16 Italian referral centres were retrospectively assessed and included in the analysis. As of March 2024, 373 ATTRv patients were in active follow-up, with an overall national prevalence increased from 2020 previous survey up to 6.33/million. The most prevalent mutations were Ile68Leu (25.1%), Phe64Leu (21.9%), Val30Met (19.3%), Glu89Gln (10.7%), and Val122Ile (6.7%). Ile68Leu, Val122Ile, and Val30Met were more common in Northern and Central Italy, while Glu89Gln and Phe64Leu were prevalent in Southern Italy. Cardiovascular phenotype was the most common (35.6%), followed by neuropathic (33.2%) and mixed phenotypes (31.2%). Referral to disease-specific therapy mirrored the change in epidemiology. Conclusion ATTRv prevalence in Italy has increased by 50% in a 4 years' time frame, with a shift towards milder disease stages and more mixed phenotypes. These changes may reflect improved disease awareness, enhanced genetic screening, and comprehensive care in specialized centres.