Familial Amyloid Polyneuropathy Associated with S50A, S52P and G47A Mutations (P03.185)

Abstract

Objective: We aim to describe the main characteristics of patients with 3 different TTR mutations. Background Familial amyloid polyneuropathy is a late-onset inherited amyloidosis associated with a mutation on the transthyretin (TTR) gene. Marked diversity exists in clinical characteristics. Design/Methods: 33 patients from 10 different families with proven TTR mutation (27 S50A, 4 S52P, and 2 G47A) underwent prospective neurologic and autonomic examination. All evaluations were performed in a period of 12 months. Results: 19 male and 14 women were included. Age at onset was later in the patients with G47A mutation (33 vs 38 vs 42 yo). S52P had more weight loss (mean of 26kg vs 12-13kg) Initial symptoms were neuropathic in 66%, gastrointestinal in 18% and autonomic in 3%. Overall, men had a more severe form of the disease and worse prognosis. Specifically, men showed more GI (15 vs 11, p:0.001), GU (4 vs 13, p:0.17), and autonomic (13 vs 5, p:0.039) symptoms, had further weight loss (13±17 vs 8±4 kg, p:0.005), orthostatic SBP fall (26±15 vs 4.5±10 mmHg, p:0.01), and decreased NCV amplitudes (sensitive median 4.40 vs 7.20mV p:0.040, sural 2.5 vs 10.4mV p:0.000, motor median 2.4 vs 4.4mV p:0.014, and tibial 2.7 vs 5.8mV p:0.000 nerves). Three men (15.7%) and one woman (7.2%) died during the study period. The men died at a younger age (44±3.5 vs 62, p:0.049). Conclusions: S52P mutation showed a more aggressive course. Because the hereditary mode is autosomal dominant, no gender differences should be expected. However, 1-2% of plasma TTR circulates bound to high-density lipoprotein (HDL). The higher HDL levels associated with estrogen could explain these differences. Men should be considered for earlier liver transplant or pharmacologic treatment when available. It is possible that measures aimed to increase HDL may have some impact in the natural history of the disease. Disclosure: Dr. Gonzalez Duarte has nothing to disclose. Dr. Cardenas-Soto has nothing to disclose. Dr. Berenguer-Sanchez has nothing to disclose. Dr. Martinez-Banos has nothing to disclose. Dr. Estanol has nothing to disclose. Dr. Garcia-Ramos has nothing to disclose. Dr. Cantu-Brito has nothing to disclose.