TRANSTHYRETIN-RELATED VARIANT AMYLOIDOSIS IN A CAUCASIAN MALE WITH TTR VAL142ILE (PREV. VAL122ILE) MUTATION.

POSADAS MARTINEZ, MARIA LOURDES; ET AL

Congreso; XVII INTERNATIONAL SYMPOSIUM ON AMYLOIDOSIS (ISA); 2020

Aguirre MA1;6, Nucifora EM2;6, Perez de Arenaza D3;6, Villanueva E3;6, Belziti C3;6, Sorroche P4;6, Saez MS4;6, Posadas-Martinez ML5;6BACKGROUND: In Argentina, there is limited data of prevalence of TTR amyloidosis, mutations or phenotype-genotype relationship. OBJECTIVES: Describe the prevalence of transthyretin genetic mutations in Argentina and the clinical characteristics of patients with hereditary TTR amyloidosis in Italian Hospital of Buenos Aires (HIBA) . METHODS: Cross sectional study of all consecutive blood samples referred to HIBA laboratory, a reference center in Argentina, for TTR gene sequencing, a reference center in Argentina, between 2012 and 2019. Our laboratory is a reference center for TTR sequencing in Argentina.Mutations in TTR were identified in peripheral blood by direct Sanger sequencing in all samples received. C but clinical characteristics were assessed only in those that were evaluated by a local physician at Italian Hospital of Buenos Aires. RESULTS: In the period of interest, 576 patients were analyzed for TTR mutations. Twenty four percent (141) were positive for a TTR mutation. The frequency distribution of the mutations were: Val50Met 78% (2% were Homozygota), Thr80Ala 11%, Ala117Ser 6%, Val142Ile 1%, Phe84Leu 1%, Ile127Val 1%, Tyr134Cys 1% and Ala56Pro 1%. Of the 141 mutated TTR patients, 20 were evaluated by a physician at HIBA. Female represented 30%, average age at diagnosis was 54 yo, 70% with family history and with a median of pedigree 4. Six different TTR variants were identified: Thr80Ala 9, Val50Met 6, Ala56Pro 2, Val142Ile 1, Phe84Leu 1 and Tyr134Cys 1. Most frequent organ involvement were: in Thr80Ala gastrointestinal 56%, cardiac 33%, neurologic 33%; in Val50Met neurologic 83%, gastrointestinal 83%, cardiac 33%, and ocular 17%; in Ala56Pro neurologic 50%, ocular 50%.The mortality rate was low of 5% (n = 1, CI 0.1% to 25%), the patient died of cardiac attack post a hepatic transplant. CONCLUSION: In our knowledge, this is the first national report of the TTR mutations epidemiology in Argentina.