Seven Years of Selective Genetic Screening Program and Follow-Up of Asymptomatic Carriers With Hereditary Transthyretin Amyloidosis in Bulgaria

• DOI: 10.3389/fneur.2022.844595
• Publication Date: 2022-04-08T07:22:49Z
• Authors: Teodora Chamova; Mariana Gospodinova; Ognian Asenov; Tihomir Todorov; Zornitsa Pavlova; Andrey Kirov; Sylvia Cherninkova; Kristina Kastreva; Ani Taneva; Stanislava Blagoeva; Sashka Zhelyazkova; Plamen Antimov; Kaloian Chobanov; Albena Todorova; Ivailo Tournev
• Keywords: Asymptomatic carrier

Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, autosomal-dominant (AD) multisystem disorder resulting from the extracellular deposition of amyloid fibrils formed by destabilized mutant form (TTR), transport protein predominantly produced liver.The aims current study are to demonstrate Bulgarian experience with screening programs among high-risk patient population over last 7 years, present results therapy TTR stabilizer in our cohort, as well stress on importance follow-up asymptomatic carriers pathogenic variants multidisciplinary team specialists.In 2014, program for ATTRv was initiated Bulgaria. On one hand, it conducted identify new patients and families people "red flag" clinical features, while other aimed mutation already genetically proven diagnoses. Sanger sequencing methodology used make fast target testing mutations gene suspected individuals. All identified underwent subsequent evaluation neurological, cardiac, gastroenterological, neuro-ophthalmological involvement. Those considered affected were provided treatment follow-up.As result 7-year selective relatives verified individuals, 340 Bulgaria following defects: 78.53% Glu89Gln, 10.29% Val30Met, 8.24% Ser77Phe, 2.06% Gly47Glu, 0.59% Ser52Pro. these displayed mixed phenotype variable ages at onset rate progression, according their mutation. From 150 treated stabilizer, 84 remained stable, 66 terminated either because polyneuropathy progression or due death. A regular 3 years enabled us detect transition 39/65 symptomatic initiate timely manner.Bulgarian display some peculiarities each that should be when treating specific defect.