Barbeau A, Roy M, Cunha L, de Vincente A N, Rosenberg R N, Nyhan W L, MacLeod P L, Chazot G, Langston L B, Dawson D M
Can J Neurol Sci. 1984 Nov;11(4 Suppl):510-25. doi: 10.1017/s0317167100034983.
We have examined 138 cases of a disorder previously described in people of Portuguese origin and which has received many names. By computer analysis of 46 different items of a standardized neurological examination carried out in each patient, we have been able to delineate the main components of the clinical presentation, to conclude that the marked variability in clinical expressions does not negate the homogeneity of the disorder, and to describe the natural history of this entity which should be called, for historical reasons, "Machado-Joseph Disease". This hereditary disease has an autosomal dominant pattern of inheritance, presenting as a progressive ataxia with external ophthalmoplegia, and should be classified within the group of "Ataxic multisystem degenerations". When the disease starts before the age of 20, it may present with marked spasticity, of a non progressive nature but often so severe that it can be accompanied by "Gegenhalten" countermovements and dystonic postures but little frank dystonia. There are few true extrapyramidal symptoms except akinesia. When the disease starts after the age of 50, the clinical spectrum is mostly that of an amyotrophic polyneuropathy with fasciculations accompanying the ataxia. For all the other cases the clinical picture is a continuum between these two extremes, the main determinant of the clinical phenotype being the age of onset and a secondary factor, the place of origin of the given kindred. The ataxic and amyotrophic components are clearly progressive with time in contrast to the spasticity component. Although the majority of known cases are of Portuguese origin, this is not obligatory. The next research endeavour should be a search for the chromosomal site of the gene, using molecular biology technology such as those for recombinant DNA.
我们已对138例曾在葡萄牙裔人群中被描述过且有多个名称的疾病病例进行了研究。通过对每位患者进行的标准化神经学检查中的46个不同项目进行计算机分析，我们得以勾勒出临床表现的主要组成部分，得出临床症状的显著变异性并不否定该疾病同质性的结论，并描述了这一疾病实体的自然史。出于历史原因，该疾病应被称为“马查多 - 约瑟夫病”。这种遗传性疾病呈常染色体显性遗传模式，表现为进行性共济失调伴眼球外肌麻痹，应归类于“共济失调性多系统变性”组。当疾病在20岁之前发病时，可能会出现明显的痉挛，这种痉挛是非进行性的，但通常非常严重，可能伴有“ gegenhalten”反向运动和张力障碍姿势，但很少有明显的肌张力障碍。除了运动不能外，几乎没有真正的锥体外系症状。当疾病在50岁之后发病时，临床谱主要是肌萎缩性多神经病伴共济失调的肌束震颤。对于所有其他病例，临床症状是这两种极端情况之间的连续体，临床表型的主要决定因素是发病年龄，次要因素是特定家族的起源地。与痉挛成分不同，共济失调和肌萎缩成分随时间明显进展性加重。尽管已知的大多数病例来自葡萄牙，但并非必须如此。接下来的研究工作应该是利用重组DNA等分子生物学技术寻找该基因的染色体位点。
