| Title: |
Detailed clinical, physiological and pathological phenotyping can impact access to disease-modifying treatments in ATTR carriers |
| Authors: |
Beauvais, Diane; Labeyrie, Céline; Cauquil, Cécile; Francou, Bruno; Eliahou, Ludivine; Not, Adeline; Echaniz-Laguna, Andoni; Adam, Clovis; Slama, Michel S; Benmalek, Anouar; Leonardi, Luca; Rouzet, Francois; Adams, David; Algalarrondo, Vincent; Beaudonnet, Guillemette |
| Publisher Information: |
BMJ Publishing Group Ltd |
| Publication Year: |
2024 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Neuromuscular |
| Description: |
Background Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic TTR variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early. Pathological nerve conduction studies (NCS) results are the cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late in the disease. We investigated the utility of a multimodal neurological and cardiac evaluation for detecting early disease onset in ATTRv carriers. Methods We retrospectively analysed a cohort of ATTRv carriers with normal NCS results regardless of symptoms. Multimodal denervation and infiltration evaluations included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) and examination, intra-epidermal nerve fibre density assessment, autonomic assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for amyloidosis on skin biopsy and bone scintigraphy. Results We included 130 ATTRv carriers (40.8% men, age: 43.6±13.5 years), with 18 amyloidogenic TTR gene mutations, the majority of which was the late-onset Val30Met variant (42.3%). Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients received DMT. Abnormal test results of unknown significance were obtained for 105 carriers (80.8%). Investigations were normal in only three carriers (2.3%). Conclusions Multimodal neurological and cardiac investigation of TTRv carriers is crucial for the early detection of ATTRv amyloidosis and initiation of DMT. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://jnnp.bmj.com/cgi/content/short/95/6/489; http://dx.doi.org/10.1136/jnnp-2023-332180 |
| DOI: |
10.1136/jnnp-2023-332180 |
| Availability: |
http://jnnp.bmj.com/cgi/content/short/95/6/489; https://doi.org/10.1136/jnnp-2023-332180 |
| Rights: |
Copyright (C) 2024, BMJ Publishing Group Ltd |
| Accession Number: |
edsbas.70644BE2 |
| Database: |
BASE |