Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier
Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier
复制标题
DOI：
10.1016/j.jns.2006.10.019
复制
发表时间：
2007-01-31
影响因子：
4.4
通讯作者：
Mizuno, Yoshikuni
中科院分区：
文献类型：
--
作者：
Kono, Satoshi;Shirakawa, Kentaro;Mizuno, Yoshikuni
戈谢病和帕金森病之间的临床联系已被证实。我们在此报告一名日本3型戈谢病患者，他的葡萄糖脑苷酶基因F2131和L444P突变是复合杂合的，而他的父亲的L444P突变是杂合的。他们都表现出帕金森病的特点，主要是动力僵硬症状，对抗帕金森治疗有良好的反应。我们使用带有放射性配体、[C-11] CFT和[C-11] raclopride的正电子发射断层扫描（PET）研究了多巴胺能神经元的功能。两例患者的PET研究显示，壳核和尾状核的[C-11] CFT摄取严重减少，但基底节区的[11C] raclopride摄取正常。虽然大多数戈谢病合并帕金森病的患者往往对抗帕金森治疗难以治愈。临床特征和PET研究结果提示，与糖脑苷酶基因突变相关的帕金森患者，甚至在杂合子中，可能与帕金森病中报道的突触前多巴胺能神经元功能障碍有关。一项评估戈谢病中多巴胺能神经元功能的PET研究将更好地了解抗帕金森疗法的效果，并有助于提高我们对戈谢病相关帕金森病的早期诊断能力。(c) 2006 Elsevier B.V.版权所有
A clinical association between Gaucher disease and parkinsonism has been demonstrated. We herein report a Japanese patient with type 3 Gaucher disease who was compound heterozygous for F2131 and L444P mutations in the glucocerebrosidase gene while his father was heterozygous for the L444P mutation. They both presented with parkinsonism characterized by a predominance of akinetic-rigid signs and a favorable response to anti-Parkinson therapies. We investigated the dopaminergic neuronal function using positron emission tomography (PET) with radioligands, [C-11] CFT and [C-11] raclopride. PET studies of both patients demonstrated the [C-11] CFT uptake to be severely decreased in the putamen and the caudate nucleus, however, the [11C] raclopride uptake was normal in the basal ganglia. Although the majority of Gaucher disease patients with parkinsonism tend to be refractory to anti-Parkinson therapies. The clinical features and the findings of the PET studies suggest that patients with parkinsonism associated with the mutation in the glucocerebrosidase gene, even in heterozygosis, may be related to the presynaptic dopaminergic neuronal dysfunction reported in Parkinson's disease. A PET study to evaluate the dopaminergic neuronal function in Gaucher disease would provide both a better understanding of the effects of anti-Parkinson therapies and a help to improve our ability to make an early diagnosis of parkinsonism associated with Gaucher disease. (c) 2006 Elsevier B.V. All rights reserved.