Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil (REACT-SP)

Abstract Background: Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. We present data on physical signs and symptoms, cardiac and neurological assessments and genetics in patients enrolled in the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil. Results: Six hundred-forty-four patients were enrolled, 505 with the variant form (ATTRv) and 139 with wild-type (ATTRwt). Sixteen different mutations were detected, the most common being Val50Met (48.3%) and V142Ile (40.8%). Overall, more than half of the patients presented cardiological involvement, and the difference in this proportion between the ATTRv and ATTRwt groups was significant (43.9 vs. 89.9%; p<0.001). The neurological phenotype also differed between ATTRv and ATTRwt (56.8 vs. 31.7%; p<0.001). The mixed phenotype was found in 25.6% of the population, without a significant difference between the forms of amyloidosis. A group of patients remained asymptomatic (10.4%), with a lower proportion of asymptomatic ATTRwt patients. Conclusions: This study details the clinical and genetic spectrum of patients with ATTR in São Paulo, Brazil. This preliminary analysis highlights the considerable phenotypic heterogeneity of neurological and cardiac manifestations in patients with variant and wild-type ATTR.