Natural History and Survival Rate of Familial Amyloidosis with Polyneuropathy: A Nationwide Databank.

Objective: Hereditary amyloid transthyretin (ATTRv) amyloidosis with poly-neuropathy, a rare autosomal-dominant disease, has gained attention in recent years owing to treatment improvements. However, epidemiological real-world mega database of nationwide natural history and survival rates, especially with the specific mutation of Ala97Ser, are limited. Methods: Taiwan National Health Insurance Research Database contains data from over 23 million individuals; Among them, 175 ATTRv amyloidosis patients validated by rare disease registry were enrolled. Multivariable Cox proportional hazard analyses were applied to investigate the association between baseline characteristics and all-cause mortality. Findings: From 2008 to 2020, the annual incidence and prevalence rates of specific mutations (Ala97Ser) leading to ATTRv amyloidosis with polyneuropathy were 0.04-1.14 and 0.04-4.79 per million in Taiwan, respectively. In Taiwan, these patients exhibited male predominance with a mean age at validation of 62.75 years. At the 5th year after validation, patients exhibited a survival rate of approximately 50%, with higher mortality in male patients (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.15-4.31) and patients older at validation (HR: 1.10, 95% CI: 1.06-1.15). The two most common departments in outpatient were neurology and family medicine, and neurology and cardiology in inpatient. The three most common causes of death registered were unspecified amyloidosis (30.6%), organ-limited amyloidosis (20.9%), and neuropathic heredofamilial amyloidosis (9.7%). Interpretation: The annual prevalence rate of specific mutation (Ala97Ser)-dominant ATTRv amyloidosis with polyneuropathy in Taiwan is comparable to the mid-to high-prevalence country level of the research by Schmidt et al. The extraordinarily high mortal-ity, especially among patients older at validation, may reflect the inadequate awareness and the necessity of early intervention with novel disease-modifying regimens.