Change in prevalence of ATTR variants in Italy - Results from a National Survey

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a rare, heterogenous, 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: All alive ATTRv diagnoses from 2004 to 2024 from 16 Italian referral centers were retrospectively assessed and included in the analysis. Results: 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 centers.