Chinnery Patrick F, Crompton Douglas E, Birchall Daniel, Jackson Margaret J, Coulthard Alan, Lombès Anne, Quinn Niall, Wills Adrian, Fletcher Nicholas, Mottershead John P, Cooper Paul, Kellett Mark, Bates David, Burn John
Institute of Human Genetics, University of Newcastle upon Tyne, UK.
Brain. 2007 Jan;130(Pt 1):110-9. doi: 10.1093/brain/awl319. Epub 2006 Dec 2.
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.
神经铁蛋白病是一种由铁蛋白轻链基因(FTL1)突变引起的、成人起病的进行性且可能可治疗的运动障碍。其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,但该疾病的表型和自然病史尚未明确。我们研究了一组基因同质的41名携带FTL1基因460InsA突变的受试者,记录了其临床表现、临床病程、生物化学和神经影像学表现。平均发病年龄为39.4岁(标准差=13.3,范围13 - 63岁),50%以舞蹈症起病,42.5%以局灶性下肢肌张力障碍起病,7.5%以帕金森综合征起病。大多数患者报告有运动障碍家族史,常被误诊为亨廷顿病。疾病无情进展,在5 - 10年内发展为全身性病变,最终导致失音、吞咽困难和严重运动功能障碍,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很常见(65%),63%的患者在整个病程中存在不对称性。大多数男性和绝经后女性血清铁蛋白水平较低,但绝经前女性在正常范围内。所有受累个体及一名症状前携带者的脑部磁共振成像均异常。总之,孤立性帕金森综合征在神经铁蛋白病中不常见,与亨廷顿病不同,早期认知改变不存在或很轻微。血清铁蛋白降低很常见,在常规实践中提供了一种有用的筛查试验,梯度回波脑磁共振成像可识别所有有症状的病例。