Objective: To describe 58 subjects with rare TTR mutations, and to compare the different biomarkers between carriers and patients.
Methods: TTR gene sequence test was performed in 15 suspicious subjects and in their direct family. All positive subjects undertook prospective evaluations in a period of 49 months.
Results: Of 95 genetic tests performed, 58 (61%) were positive for TTR mutations, Ser50Arg mutation in 38 (65%), Ser52Pro in 15 (26%) and Gly47Ala in 5 (9%). Initial symptoms were neuropathic in 19 (73%), gastrointestinal in 6 (23%) and autonomic in 1 (4%).
Conclusions: The natural history of Ser50Arg, Ser52Pro and Gly47Ala TTR mutations is similar to the Val30Met mutation described in endemic areas. The small fiber assessments were the initial tests to show abnormalities in asymptomatic subjects.