摘要
目的 探讨转甲蛋白相关家族性淀粉样周围神经病（TTR-FAP）患者的临床、电生理、组织病理和遗传学表现.方法 对北京协和医院2006-2014年确诊的13个家系（先证者）和散发TTR-FAP病例进行临床观察、分期、系统评估和随访.对其中12例进行了周围神经和（或）肌肉活组织检查（活检）,主要采用腓浅神经与腓骨短肌联合活检.同时采用转甲蛋白免疫组织化学染色和转甲蛋白基因检测.结果 （1）临床表现：13例先证者和散发病例,男性11例,女性2例,发病年龄17 ～53岁,平均37.7岁.5例以周围神经病起病;4例以晕厥和（或）短暂脑缺血发作样症状起病;4例以腹泻起病.从发病到确诊的平均时间为2.96年.全部患者均有感觉和运动性周围神经病和自主神经功能障碍.临床分期1期4例,2期5例,3期4例.（2）神经肌肉活检病理：周围神经病理改变为慢性活动性轴索性损害,肌肉病理改变以神经源性损害为主,刚果红和转甲蛋白免疫组织化学染色阳性,提示转甲蛋白阳性物质淀粉样物质在神经与肌肉中沉积.（3）基因检测发现10种点突变,其中E54Q点突变未见报道.（4）诊疗与转归：对全部患者予维生素营养神经治疗,3例近期予二氟尼柳治疗,5例于发病后3～6年死亡.结论 TTR-FAP呈现基因型和临床表型的多样性,经典的V30M型在我国可能不是优势类型.本组病例以早发型为主,部分患者进展迅速,可能与特定的基因突变类型有关.神经肌肉联合活检加转甲蛋白免疫组织化学染色可提供TTR-FAP组织学确诊证据.
Objective To investigate the clinical,electrophysiological,histopathological and genetic findings in patients with transthyretin （TTR）-associated familial amyloid polyneuropathy （FAP） （TTR-FAP） in China.Methods Familial or sporadic cases of TTR-FAP of Chinese Han orgin diagnosed at Peking Union Medical College Hospital in the past eight years （2006-2014） were retrospectively reviewed.Clinical,neuropathological and genetic characteristics of these patients were evaluated.Results Thirteen cases with TTR-FAP diagnosed by pathology and genetic screening were collected.Clinically,all patients exhibited distal symmetric motor and sensory neuropathy with sensory loss of the lower and upper limbs.Five patients experienced muscle pain,2 had transient ischemic attack and all had various autonomic involvements.Other affected organs include cardiomyopathy in 12 cases,thyroid infiltration in 3 cases and leptomeningeal enhancement in 4.Nerve conduction studies showed sensorimotor axonal neuropathy in all patients.Histologically,5 of 10 patients were found amyloid deposit in peripheral nerve.All the cases were positive for muscular amyloid and TTR immuonstaining.TTR-positive amyloid deposits were detected in 5 of 11 patients who performed peripheral nerve biopsy and in all the 10 cases that performed muscle TTR staining.Genetically,of the 13 TTR-FAP patients,9 reported and one novel TTR mutations （E54Q） were identified in the TTR gene.Conclusions TTR-FAP may be under-diagnosed in Chinese population and should be considered in patients with chronic progressive neuropathy accompanied by multisystem involvements.Combined biopsy of peroneus brevis muscle and superficial peroneal nerve might be a prime choice to get positive pathological findings.Genetic screening is mandatory but no specific genotypephenotype correlations should be expected.G47R may be the most common mutation in Chinese FAP cases.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2015年第1期7-12,共6页
Chinese Journal of Neurology
