ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
This article is part of the Research TopicThe Regeneration and Intervention of Neurological Tissue after Acute and Chronic Injuries: from Benchside to BedsideView all 9 articles
Clinical and Genetic Features of Hereditary Transthyretin Amyloidosis with Polyneuropathy in China: Insights from Case Analysis and Literature Review
Provisionally accepted
- 1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China
- 2Department of Neurology, Hebei Hospital of Xuanwu Hospital Capital Medical University, Shijiazhuang, China
- 3Department of Minimally Invasive Spine Surgery, Hebei Hospital of Xuanwu Hospital Capital Medical University, Shijiazhuang, China
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Abstract Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive multisystem disorder caused by pathogenic TTR variants. Aim of this study is to delineate the clinical and genetic feature of ATTRv-PN in China and to evaluate diagnostic strategies for earlier and accurate recognition. Methods: We investigated two genetically confirmed Chinese patients with ATTRv-PN through comprehensive assessments, including electrophysiology, sural nerve biopsy, autonomic testing, cardiac imaging, neuroimaging, and cerebrospinal fluid analysis. Additionally, logistic regression was performed on 70 reported p.Val50Met cases to examine the relationship between age at onset and amyloid detection in sural nerve biopsies. Results: The two patients carried the p.Val50Met and p.Glu74Gly variants in the TTR gene, respectively. Both presented with distal paresthesia as the initial symptom and exhibited length-dependent, axonal-predominant sensorimotor polyneuropathy. Autonomic manifestations included alternating diarrhea/constipation and post-exertional hyperhidrosis. Subclinical cardiac abnormalities were identified, encompassing elevated biomarker of early cardiac strain, valvular regurgitation, left ventricular hypertrophy, and late gadolinium enhancement. In patient 1, sural nerve pathology showed marked loss of myelinated and unmyelinated fibers with perivascular lymphocytic infiltration but no amyloid deposition. Logistic regression revealed no significant association between age at onset and biopsy amyloid positivity (p = 0.91). 3 Conclusions: This study expands the clinical and genetic landscape of ATTRv-PN in China and highlighted the heterogeneity of amyloid detection in nerve biopsies. Accurate and timely diagnosis requires an integrated approach combining clinical, electrophysiological, pathological, genetic, and multimodal imaging assessments to facilitate early initiation of disease-modifying therapies.
Keywords: ATTRv-PN, hereditary transthyretin amyloidosis, polyneuropathy, Sural nerve biopsy, TTR
Received: 07 Oct 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 Yuan, Lv, Wang, Han and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bingchuan Xie
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