Neuropathy in Val122Ile Hereditary Transthyretin ( ATTR ) Amyloidosis: A Multicenter Retrospective Cohort Study

BACKGROUND AND AIMS: The Val122Ile ATTR Amyloidosis has traditionally been linked to cardiac manifestations. Recent studies suggest that neuropathy may be relevant. In this study, we characterized its peripheral nerve manifestations in depth. METHODS: This was a national, multicenter, observational, retrospective study. Patients underwent careful clinical and neurophysiological evaluation. We excluded those with alternative etiologies. RESULTS: We identified 246 Val122Ile carriers, including 240 heterozygous, 4 homozygous, and 2 compound heterozygous. Gender distribution was similar. Age of onset: 19-89 years, mean 53 ± 17. Self-reported ethnicity: White (26.7%), Black (17.3%), and Mixed (Pardo) (56.0%). Birthplaces spanned all Brazilian regions, mainly the Northeast. Among heterozygotes, 52 of 122 (42.6%) were symptomatic. Carpal tunnel syndrome (CTS) preceded polyneuropathy and/or cardiomyopathy in 69.2%. The most frequent onset manifestations, excluding CTS, were cardiomyopathy (52.9%), neuropathy (37.3%), and mixed phenotype (9.8%). Age of onset: 29-86 years (mean: 64.9 years). During follow-up, 14/27 cardiac patients developed neuropathy, and 8/19 neurologic patients developed cardiomyopathy, significantly increasing the mixed phenotype from 9.8% to 52.9%. Most patients with neuropathy presented with sensory or sensory and motor disease (62.2%), followed by small fiber neuropathy (32.4%), and isolated dysautonomia (5.4%). INTERPRETATION: Neuropathy is underrecognized in Val122Ile ATTR Amyloidosis, is frequent at disease onset, may be the sole manifestation, and may occur in White persons. CTS frequently preceded neuropathy, usually an axonal polyneuropathy, although atypical patterns were observed. This variant clusters in the Northeast region of Brazil.

Authors

Institutions

Publication Details

Journal
Journal of the Peripheral Nervous System
Published
2026-08-28
DOI
https://doi.org/10.1111/jns.70160
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Neuropathy in Val122Ile Hereditary Transthyretin ( ATTR ) Amyloidosis: A Multicenter Retrospective Cohort Study

Carlo Domênico Marrone, Marcondes C. França, Anna Paula Paranhos Miranda Covaleski, Lara Albuquerque de Brito et al.
Journal of the Peripheral Nervous System
Amyloidosis: Diagnosis, Treatment, Outcomes
article

Neuropathy in Val122Ile Hereditary Transthyretin ( ATTR ) Amyloidosis: A Multicenter Retrospective Cohort Study

Carlo Domênico Marrone, Marcondes C. França, Anna Paula Paranhos Miranda Covaleski, Lara Albuquerque de Brito, Eduardo Boiteux Uchôa Cavalcanti, Osvaldo J. M. Nascimento, Diogo Fernandes dos Santos, Wilson Marques, Pedro José Tomaselli, Marcela Câmara Machado‐Costa, Marcelo Soares Kerstenetzky, Ândrea Virgínia Chaves-Markman, Carolina Lavigne Moreira, Cleonísio Leite Rodrigues, Jemima Araújo da Silva Batista, Marcus Vinícius Magno Gonçalves, Renan Flávio de França Nunes
article en

Abstract

BACKGROUND AND AIMS: The Val122Ile ATTR Amyloidosis has traditionally been linked to cardiac manifestations. Recent studies suggest that neuropathy may be relevant. In this study, we characterized its peripheral nerve manifestations in depth. METHODS: This was a national, multicenter, observational, retrospective study. Patients underwent careful clinical and neurophysiological evaluation. We excluded those with alternative etiologies. RESULTS: We identified 246 Val122Ile carriers, including 240 heterozygous, 4 homozygous, and 2 compound heterozygous. Gender distribution was similar. Age of onset: 19-89 years, mean 53 ± 17. Self-reported ethnicity: White (26.7%), Black (17.3%), and Mixed (Pardo) (56.0%). Birthplaces spanned all Brazilian regions, mainly the Northeast. Among heterozygotes, 52 of 122 (42.6%) were symptomatic. Carpal tunnel syndrome (CTS) preceded polyneuropathy and/or cardiomyopathy in 69.2%. The most frequent onset manifestations, excluding CTS, were cardiomyopathy (52.9%), neuropathy (37.3%), and mixed phenotype (9.8%). Age of onset: 29-86 years (mean: 64.9 years). During follow-up, 14/27 cardiac patients developed neuropathy, and 8/19 neurologic patients developed cardiomyopathy, significantly increasing the mixed phenotype from 9.8% to 52.9%. Most patients with neuropathy presented with sensory or sensory and motor disease (62.2%), followed by small fiber neuropathy (32.4%), and isolated dysautonomia (5.4%). INTERPRETATION: Neuropathy is underrecognized in Val122Ile ATTR Amyloidosis, is frequent at disease onset, may be the sole manifestation, and may occur in White persons. CTS frequently preceded neuropathy, usually an axonal polyneuropathy, although atypical patterns were observed. This variant clusters in the Northeast region of Brazil.

Journal of the Peripheral Nervous SystemVol. 31(3)
Escola Bahiana de Medicina e Saúde Pública (BR), Universidade de Ribeirão Preto (BR), Universidade Federal Fluminense (BR), Universidade de São Paulo (BR), Universidade Estadual de Campinas (UNICAMP) (BR), Governo do Distrito Federal (BR), Instituto de Saúde (BR), Hospital São Lucas da PUCRS (BR), Hospital das Clínicas da Universidade Federal de Pernambuco (BR), Hospital de Clínicas da Unicamp (BR), Hospital Geral de Fortaleza (BR), Universidade Federal do Vale do São Francisco (BR), Universidade de Pernambuco (BR), Universidade Federal de Uberlândia (BR)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico
Gender equality
Openalex Percentile: Top 17%
Amyloidosis: Diagnosis, Treatment, Outcomes
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.