Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation
Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation
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DOI：
10.1093/brain/awl319
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发表时间：
2007-01-01
期刊：
影响因子：
14.5
通讯作者：
Burn, John
中科院分区：
文献类型：
--
作者：
Chinnery, Patrick F.;Crompton, Douglas E.;Burn, John
神经铁蛋白病是一种进行性的、有可能治疗的成人起病运动障碍，由铁蛋白轻链基因(FTL1)突变引起。特征与常见的锥体外系疾病重叠：特发性扭转肌张力障碍，特发性帕金森病和亨廷顿病，但表型和自然病史尚未确定。我们研究了41名具有FTL1基因460InsA突变的遗传同质性受试者，记录了他们的表现、临床病程、生化和神经成像。平均发病年龄39.4岁(SD=13.3，13~63岁)，首发舞蹈症占50%，局灶性下肢肌张力障碍占42.5%，帕金森综合征占7.5%。大多数人报告了一种运动障碍的家族史，经常被误诊为亨廷顿氏病。这种疾病不断发展，在5-10年期间变得普遍，最终导致失音、吞咽困难和严重的运动障碍，并以皮质下/额叶认知功能障碍为晚期特征。特征性的动作特异性面部肌张力障碍是常见的(65%)，63%的患者在整个病程中存在不对称。大多数男性和绝经后女性的血清铁蛋白水平较低，但绝经前女性的血清铁蛋白水平在正常范围内。所有患者和一名症状前携带者的磁共振脑成像均异常。总而言之，孤立性帕金森病在神经性铁蛋白病变中并不常见，而且与亨廷顿病不同的是，早期的认知改变是不存在的或微妙的。血清铁蛋白降低是常见的，在常规实践中提供了一种有用的筛查测试，而梯度回波脑部MRI将识别所有有症状的病例。
Neuroferritinopathy is a progressive potentially treatable adult-onset movement disorder caused by mutations in the ferritin light chain gene (FTL1). Features overlap with common extrapyramidal disorders: idiopathic torsion dystonia, idiopathic Parkinson's disease and Huntington's disease, but the phenotype and natural history have not been defined. We studied a genetically homogeneous group of 41 subjects with the 460InsA mutation in FTL1, documenting the presentation, clinical course, biochemistry and neuroimaging. The mean age of onset was 39.4 years (SD = 13.3, range 13-63), beginning with chorea in 50%, focal lower limb dystonia in 42.5% and parkinsonism in 7.5%. The majority reported a family history of a movement disorder often misdiagnosed as Huntington's disease. The disease progressed relentlessly, becoming generalized over a 5-10 year period, eventually leading to aphonia, dysphagia and severe motor disability with subcortical/frontal cognitive dysfunction as a late feature. A characteristic action-specific facial dystonia was common (65%), and in 63% there was asymmetry throughout the disease course. Serum ferritin levels were low in the majority of males and post-menopausal females, but within normal limits for pre-menopausal females. MR brain imaging was abnormal on all affected individuals and one presymptomatic carrier. In conclusion, isolated parkinsonism is unusual in neuroferritinopathy, and unlike Huntington's disease, cognitive changes are absent or subtle in the early stages. Depressed serum ferritin is common and provides a useful screening test in routine practice, and gradient echo brain MRI will identify all symptomatic cases.