皮肤活检作为英国遗传性转甲状腺素蛋白淀粉样变神经病的诊断工具
Skin Biopsy as a Diagnostic Tool for ATTRv Amyloid Neuropathy in the UK.
作者信息
O'Donnell Luke F, Zhang Victor, Carganillo Roy, Rossor Alexander M, Laura Matilde, Skorupinska Mariola, Gilbertson Janet A, Rowczenio Dorota, Razvi Yousuf, Gillmore Julian D, Reilly Mary M
机构信息
Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
National Amyloidosis Centre, University College London, London, UK.
出版信息
J Peripher Nerv Syst. 2025 Sep;30(3):e70042. doi: 10.1111/jns.70042.
OBJECTIVE
Gene silencing therapy for ATTRv has revolutionised treatment. In minimally symptomatic, early neuropathic disease, skin biopsy can aid in the diagnosis of ATTRv-PN, assessing both amyloid deposition and IENFD. Our aim was to study the value of performing skin biopsies in the diagnosis of ATTRv-PN in UK patients and to assess the influence of this on accessing gene silencing treatment.
METHODS
Seventy-three patients had skin biopsies performed between July 2021 and October 2023. These were stained for amyloid, typed by immunohistochemistry, and analysed for IENFD.
RESULTS
The Thr60Ala (30%), Val122Ile (23%) and Val30Met (22%) variants represented the largest number of cases. Normal/equivocal neurophysiology was demonstrated in 78% of cases. 40% of patients had abnormal IENFD, 33% had positive amyloid and 16% had both. This allowed 33% of patients to start gene silencing therapy, 75% of whom had a preceding amyloid cardiomyopathy diagnosed.
CONCLUSIONS
Skin biopsy is a useful, minimally invasive method for diagnosing ATTRv-PN. It allowed a substantial number of patients to commence gene silencing treatment. As Thr60Ala and Val122Ile are the commonest TTR variants in the UK and patients often present with cardiomyopathy, early diagnosis of ATTRv-PN is critical for treatment decisions.
目的
针对转甲状腺素蛋白淀粉样变性（ATTRv）的基因沉默疗法彻底改变了治疗方式。在症状轻微的早期神经病变疾病中，皮肤活检有助于ATTRv周围神经病（ATTRv-PN）的诊断，可同时评估淀粉样蛋白沉积和表皮内神经纤维密度（IENFD）。我们的目的是研究在英国患者中进行皮肤活检对ATTRv-PN诊断的价值，并评估其对获得基因沉默治疗的影响。
方法
2021年7月至2023年10月期间，对73例患者进行了皮肤活检。对活检样本进行淀粉样蛋白染色、免疫组织化学分型，并分析IENFD。
结果
Thr60Ala（30%）、Val122Ile（23%）和Val30Met（22%）变异型病例数最多。78%的病例神经生理学检查结果正常/不明确。40%的患者IENFD异常，33%的患者淀粉样蛋白呈阳性，16%的患者两者均异常。这使得33%的患者能够开始基因沉默治疗，其中75%的患者之前被诊断患有淀粉样心肌病。
结论
皮肤活检是诊断ATTRv-PN的一种有用的微创方法。它使大量患者能够开始基因沉默治疗。由于Thr60Ala和Val122Ile是英国最常见的转甲状腺素蛋白（TTR）变异型，且患者常伴有心肌病，因此ATTRv-PN的早期诊断对于治疗决策至关重要。
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