Brüggemann Norbert, Hagenah Johann, Reetz Kathrin, Schmidt Alexander, Kasten Meike, Buchmann Inga, Eckerle Susanne, Bähre Manfred, Münchau Alexander, Djarmati Ana, van der Vegt Joyce, Siebner Hartwig, Binkofski Ferdinand, Ramirez Alfredo, Behrens Maria I, Klein Christine
Schilling Section of Clinical and Molecular Neurogenetics and Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Arch Neurol. 2010 Nov;67(11):1357-63. doi: 10.1001/archneurol.2010.281.
To determine clinical features and to identify changes in brain structure and function in compound heterozygous and heterozygous ATP13A2 mutation carriers.
Prospective multimodal clinical and neuroimaging study.
University of Lübeck, Lübeck, Germany.
Eight family members of a large Chilean pedigree with Kufor-Rakeb syndrome (KRS).
Clinical characterization, dopamine transporter (DAT) imaging, voxel-based morphometry (VBM), and transcranial sonography (TCS).
Frequency of parkinsonian signs, brain structure, and functional alterations.
The only available patient with compound heterozygous KRS showed a markedly reduced striatal DAT density bilaterally. Magnetic resonance imaging revealed severe global brain atrophy as well as iron deposition in the basal ganglia. The heterozygous mother had definite parkinsonism with reduced DAT density in both putamina. While all asymptomatic heterozygous siblings displayed subtle extrapyramidal signs, DAT imaging revealed striatal tracer uptake within physiological levels. Voxel-based morphometry revealed an increase in gray matter volume in the right putamen and a decrease in the cerebellum of the heterozygous carriers. In all mutation carriers, the substantia nigra had a normal appearance on TCS.
Single ATP13A2 heterozygous mutations may be associated with clinical signs of parkinsonism and contribute to structural and functional brain changes. Lack of hyperechogenicity in the substantia nigra may be a distinctive feature of this form of genetic parkinsonism. This, along with the finding of iron in the basal ganglia in our patient with KRS, implies a different underlying pathophysiology compared with other monogenic forms of parkinsonism and idiopathic PD and may place KRS among the syndromes of neurodegeneration with brain iron accumulation (NBIA).
确定复合杂合子和杂合子ATP13A2突变携带者的临床特征，并识别其脑结构和功能的变化。
前瞻性多模态临床和神经影像学研究。
德国吕贝克吕贝克大学。
来自一个患有库福-拉凯布综合征（KRS）的大型智利家系的8名家庭成员。
临床特征描述、多巴胺转运体（DAT）成像、基于体素的形态学测量（VBM）和经颅超声检查（TCS）。
帕金森体征的频率、脑结构和功能改变。
唯一一名复合杂合子KRS患者双侧纹状体DAT密度显著降低。磁共振成像显示严重的全脑萎缩以及基底节铁沉积。杂合子母亲有明确的帕金森症，双侧壳核DAT密度降低。虽然所有无症状的杂合子兄弟姐妹都表现出轻微的锥体外系体征，但DAT成像显示纹状体示踪剂摄取在生理水平范围内。基于体素的形态学测量显示杂合子携带者右侧壳核灰质体积增加，小脑体积减小。在所有突变携带者中，黑质在TCS上外观正常。
单个ATP13A2杂合子突变可能与帕金森症的临床体征相关，并导致脑结构和功能改变。黑质缺乏高回声可能是这种遗传性帕金森症的一个显著特征。这一点，连同我们的KRS患者基底节中铁的发现，意味着与其他单基因形式的帕金森症和特发性帕金森病相比，其潜在的病理生理学不同，并且可能使KRS属于脑铁沉积神经变性综合征（NBIA）。
