Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis

The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain. Patients wit...

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Authors: De Frutos, Fernando|||0000-0003-4350-3217, Ochoa, Juan Pablo|||0000-0002-7966-0313, Gómez-González, Cristina, Reyes-Leiva, David|||0000-0001-6983-7130, Aróstegui, Juan Ignacio|||0000-0003-4757-504X, Casasnovas, Carlos|||0000-0002-7933-4681, Barriales-Villa, Roberto|||0000-0002-6721-3487, Sevilla, Teresa|||0000-0003-4716-2667, Gonzalez-Lopez, Esther, Ramil, Elvira, Galan, Lucia, González-Costello, José|||0000-0002-7437-3630, García-Álvarez, Ana|||0000-0002-1718-2424, Rojas-Garcia, Ricard|||0000-0003-1411-5573, Espinosa, Maria Angeles, García-Pavía, Pablo|||0000-0002-5470-2257
Format: article
Publication Date:2023
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:301697
Online Access:https://ddd.uab.cat/record/301697
https://dx.doi.org/urn:doi:10.1080/13506129.2022.2142110
Access Level:Open access
Keyword:Amyloidosis
Glu89Lys
Founder effect
Hereditary ATTR
Transthyretin
Description
Summary:The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain. Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals. Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7-9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis (p < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain. Glu89Lys ATTRv is a TTR variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.

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