ATTRv amyloidosis Italian Registry: clinical and epidemiological data

ATTRv amyloidosis is worldwide spread with endemic foci in Portugal and Sweden, Japan, Brazil, Maiorca, and Cyprus. A national Registry was developed to characterise the epidemiology and genotype-phenotype correlation of ATTRv amyloidosis in Italy and to allow a better planning of diagnostic and therapeutic services. Fifteen Italian referral centres for amyloidosis spread all over the country have contributed to the Registry. Four-hundred-forty-seven subjects were enrolled, 187 asymptomatic carriers and 260 affected patients. Thirty-one different mutations were recorded. The seven most represented genetic variants were significantly different in terms of age at onset, clinical features and geographical distribution. National prevalence is 4.33/million with higher values in Southern Italy. Overall symptoms of polyneuropathy were present at disease onset in about half of the patients, symptoms of cardiomyopathy in a quarter of patients, the rest referring carpal tunnel syndrome, dysautonomia or lumbar spinal stenosis. 52.6% of patients were in FAP stage 1, 20.4% in stage 2 and 13.5% in stage 3, while 13.5% patients had no neuropathy, presenting only cardiological symptoms. We presented an epidemiological study based on collaboration among referral centres for ATTRv amyloidosis spread in all the Italian territory, using web-based Registry. It provided a detailed map of the regional distribution of the disease. The increased awareness of the disease among general practitioners and medical specialists has contributed to reduce the diagnostic delay and the rate of misdiagnosis. The Registry will allow to collect also future information about clinical and instrumental follow-up.

ATTRv淀粉样变（ATTRv amyloidosis）呈全球分布，在葡萄牙、瑞典、日本、巴西、马略卡岛及塞浦路斯存在地方性流行灶。为明确意大利境内ATTRv淀粉样变的流行病学特征及基因型-表型关联，并优化诊疗服务的规划布局，研究者搭建了全国性登记注册系统。全国15家分布于各地的淀粉样变转诊中心参与了该登记系统的数据贡献工作。本次研究共纳入447名受试者，其中187名为无症状携带者，260名为发病患者。研究共记录到31种不同的突变类型，其中7种最常见的遗传变异在发病年龄、临床特征及地域分布上存在显著差异。该疾病的全国患病率为4.33/百万，在意大利南部地区患病率更高。约半数患者在发病初期即出现多发性周围神经病变症状，四分之一患者出现心肌病相关症状，剩余患者则以腕管综合征、自主神经功能障碍或腰椎椎管狭窄为首发表现。52.6%的患者处于家族性淀粉样多神经病（familial amyloid polyneuropathy, FAP）1期，20.4%处于2期，13.5%处于3期；另有13.5%的患者无周围神经病变，仅表现为心脏相关症状。本研究依托覆盖意大利全境的ATTRv淀粉样变转诊中心协作网络，采用基于网络的登记注册系统开展了一项流行病学调查，清晰绘制了该疾病的区域分布图谱。全科医师及专科医师对该病认知度的提升，有助于缩短诊断延迟时间并降低误诊率。该登记系统未来还可用于收集患者的临床及辅助检查随访数据。