Progressive cerebellar ataxia, proximal neurogenic weakness and ocular motor disturbances: Hexosaminidase A deficiency with late clinical onset in four siblings
Progressive cerebellar ataxia, proximal neurogenic weakness and ocular motor disturbances: Hexosaminidase A deficiency with late clinical onset in four siblings
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DOI：
10.1016/s0022-510x(96)00233-x
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发表时间：
1997-01-01
影响因子：
4.4
通讯作者：
Meinck, HM
中科院分区：
文献类型：
--
作者：
Hund, E;Grau, A;Meinck, HM
泰-萨二氏病是由编码β-D-N-乙酰氨基己糖苷酶α-亚基的氨基己糖苷酶（Hex）A基因突变引起的遗传决定的神经退行性疾病。在临床上，有严重的脑脊髓病导致死亡的头几年内的生活。这些患者的组织和体液中通常不存在Hex A活性。青少年和成人Hex A缺乏症不太严重，但罕见的变异与一些残留的Hex A活性。所有这些变体在德系犹太人中最为普遍。我们描述了一个非犹太家庭，其中四个成年的兄弟姐妹篇有显着减少十六进制A活动和发病的症状，在第二个十年的生活。表型表达是非常均匀的，包括在缓慢进行性运动神经元疾病，共济失调和眼运动障碍的组合。没有一个病人在他们的疾病的这个阶段痴呆。磁共振检查显示严重的小脑萎缩，但其他方面正常。通过使用荧光底物4-MUG和4-MUGS在血清和皮肤成纤维细胞中进行生化测量以及通过凝胶电泳确定Hex A缺乏。分子遗传学研究表明，患者是“成人”突变Gly（269）-> Ser和Hex A基因外显子11中“婴儿”4-碱基插入的复合杂合子。(C)1997年Elsevier Science B.V.
Tay-Sachs disease is a genetically determined neurodegenerative disorder, resulting from mutations of the hexosaminidase (Hex) A gene coding for the alpha-subunit of beta-D-N-acetyl-hexosaminidase. Clinically, there is severe encephalomyelopathy leading to death within the first few years of life. Hex A activity is usually absent in tissue and body fluids of these patients. Juvenile and adult Hex A deficiencies are less severe but rare variants with some residual Hex A activity. All these variants are most prevalent among Ashkenazi Jews. We describe a non-Jewish family in which four adult brothers and sisters had markedly reduced Hex A activities and onset of symptoms in the second decade of life. The phenotypical expression was remarkably homogeneous, consisting in a combination of slowly progressive motor neuron disease, ataxia and ocular motor disturbances. None of the patients were demented at this stage of their illness. Magnetic resonance studies showed severe cerebellar atrophy, but were otherwise normal. Hex A deficiency was established by biochemical measurements in the serum and skin fibroblasts using the fluorogenic substrates 4-MUG and 4-MUGS as well as by gel electrophoresis. Molecular genetic studies revealed that the patients are compound heterozygotes for the 'adult' mutation Gly(269) --> Ser and the 'infantile' 4-base insertion in exon 11 of the Hex A gene. (C) 1997 Elsevier Science B.V.