Clinical and genetic features of hereditary transthyretin amyloidosis with polyneuropathy in China: insights from case analysis and literature review

BackgroundHereditary 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.MethodsWe 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.ResultsThe 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).ConclusionThis 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.