CENTOGENE GmbH, Rostock, Germany.
Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Ann Med. 2021 Dec;53(1):1787-1796. doi: 10.1080/07853890.2021.1988696.
Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4-5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology.
A multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"-TRAM study was performed in Germany, Austria, and Switzerland.
A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various variants (-positive) were identified. Body Mass Index was lower in the -positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in -positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in -positive patients.
Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis" TRAM study and screened for pathogenic variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.
遗传性转甲状腺素蛋白相关淀粉样变性是一种临床异质性常染色体显性遗传病，由 基因中的致病性变异引起，其特征是不溶性错误折叠蛋白纤维的沉积。由于临床异质性，诊断通常会延迟 4-5 年；误诊很常见。本研究的目的是确定无明显病因的多发性神经病和/或心肌病患者中遗传性转甲状腺素蛋白相关淀粉样变性的患病率。
在德国、奥地利和瑞士进行了一项多中心观察性“遗传性转甲状腺素蛋白相关淀粉样变性的流行病学分析”-TRAM 研究。
共有 5141 名参与者由 50 个神经病学和 27 个心脏病学专业中心招募。遗传分析显示，无明显病因的多发性神经病和/或心肌病患者中，遗传性转甲状腺素蛋白相关淀粉样变性的阳性率为 1.1%。共发现 21 种不同的 变体（-阳性）。-阳性患者的体重指数较低，这表明其自主神经系统受累；-阳性患者的临床表现发病年龄较高。-阳性患者没有其他基因型-表型相关性或特定临床表现的患病率。
我们的数据支持这样一个事实，即遗传性转甲状腺素蛋白相关淀粉样变性在多发性神经病和心肌病患者中被漏诊。建议对不明原因多发性神经病和/或心肌病患者常规进行基因检测，以加速早期诊断和及时开始治疗。
在观察性“遗传性转甲状腺素蛋白相关淀粉样变性的流行病学分析”TRAM 研究中，招募了 5000 多名病因不明的 CM 和/或 PNP 患者，并对其进行了致病性 变体筛查。该研究表明，病因不明的 CM 和/或 PNP 患者中，有>1%的患者携带致病性 变体。建议对不明原因的 CM 和/或 PNP 患者进行常规基因检测，以加速初始诊断和及时治疗。
