• Teresa Coelho, Isabel Conceição, Márcia Waddington-Cruz, Denis Keohane, Marla B Sultan, Doug Chapman, Leslie Amass, and THAOS investigators.
• Unidade Corino Andrade, Hospital Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal.
• Amyloid. 2022 Dec 1; 29 (4): 228236228-236.

BackgroundHereditary transthyretin amyloidosis (ATTRv amyloidosis) results from pathogenic mutations in the transthyretin (TTR) gene. This analysis aimed to better understand ATTRv amyloidosis development in asymptomatic TTR gene carriers.MethodsThe Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic TTR gene carriers. Asymptomatic TTR gene carriers were assessed longitudinally to identify those who developed ATTRv amyloidosis after enrolment in THAOS (data cut-off: 1 August 2021).ResultsOf 740 asymptomatic TTR gene carriers, 268 (36.2%) (Val30Met, 212/613 [34.6%]; non-Val30Met, 48/111 [43.2%]) developed ATTRv amyloidosis within a median 2.2 years after enrolment. The most common first symptoms were sensory (49.5%) and autonomic (37.3%) neuropathy in Val30Met patients, and sensory neuropathy (45.8%) and cardiac disorder (22.9%) in non-Val30Met patients. Most patients first presented with a predominantly neurologic phenotype (Val30Met, 77.8%; non-Val30Met, 70.8%).ConclusionsMore than one-third of asymptomatic TTR gene carriers in THAOS developed ATTRv amyloidosis within a median 2 years of enrolment. Val30Met versus non-Val30Met patients had a lower transition rate. Given the importance of early treatment, these findings underscore the need for identification and careful monitoring of at-risk TTR gene carriers to enable prompt treatment.Trial RegistrationClinicalTrials.gov: NCT00628745.

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