Autosomal dominant juvenile amyotrophic lateral sclerosis
Autosomal dominant juvenile amyotrophic lateral sclerosis
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DOI：
10.1093/brain/122.8.1539
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发表时间：
1999-08-01
期刊：
影响因子：
14.5
通讯作者：
Cornblath, DR
中科院分区：
文献类型：
--
作者：
Rabin, BA;Griffin, JW;Cornblath, DR
幼年型肌萎缩侧索硬化症（ALS）是一种慢性运动神经元疾病，其特征在于在25岁之前发作的上和下运动神经元症状和体征的组合。我们报告的临床和电诊断结果在49个受影响的家庭成员和神经病理学结果从两个尸检的马里兰州亲属与常染色体显性青少年ALS连锁的染色体9 q34区域（ALS 4）。患者年龄范围为12 - 85岁（平均45岁），平均发病年龄为17岁。远端无力和萎缩与锥体束征（43/49）和正常感觉（44/49）相关。运动传导研究（n = 8）显示诱发振幅降低，传导参数正常。所有受试患者的感觉传导研究（n = 8）、定量感觉测试（n = 4）和皮肤活检皮内感觉纤维（n = 6）均正常。肌电图显示远端多于近端慢性部分失神经支配和神经再支配（n = 8）。尸检脊髓组织显示脊髓萎缩，前角细胞明显丢失，皮质脊髓束变性，以及背根神经节神经元丢失和后柱变性。轴突球体存在于脊髓灰质、背根进入区和周围神经中。运动和感觉根，以及周围神经，表现出显着的轴突损失。在运动神经元周围有突出的突起，可能代表突触前末梢的变化。这些研究定义了与染色体9 q34区域（ALS 4）相关的常染色体显性青少年ALS，并扩展了家族性ALS和青少年ALS的临床、病理和遗传异质性。
Juvenile amyotrophic lateral sclerosis (ALS) is a form of chronic motor neuron disease characterized by combined upper and lower motor neuron symptoms and signs with onset prior to age 25 years. We report the clinical and electrodiagnostic findings in 49 affected family members and neuropathological findings from two autopsies of a Maryland kindred with autosomal dominant juvenile ALS linked to the chromosome 9q34 region (ALS4). Patients ranged in age from 12 to 85 years (mean 45 years) and the mean age of onset was 17 years. Distal weakness and atrophy was associated with pyramidal signs (43/49) and normal sensation (44/49). Motor conduction studies (n = 8) showed reduced evoked amplitudes and normal conduction parameters. Sensory conduction studies (n = 8), quantitative sensory testing (n = 4) and intracutaneous sensory fibres in skin biopsies (n = 6) were normal in all patients tested. Electromyography showed distal more than proximal chronic partial denervation and reinnervation (n = 8). Post-mortem spinal cord tissue demonstrated atrophic spinal cords with marked loss of anterior horn cells and degeneration of corticospinal tracts, as well as loss of neurons in the dorsal root ganglia and degeneration of the posterior columns. Axonal spheroids were present in the grey matter of the spinal cord, the dorsal root entry zones and the peripheral nerves. Motor and sensory roots, as well as peripheral nerves, showed significant axonal loss. Swellings were prominent around motor neurons, probably representing changes in presynaptic terminals. These studies define autosomal dominant juvenile ALS linked to the chromosome 9q34 region (ALS4) and extend the clinical, pathological and genetic heterogeneity of familial ALS and juvenile ALS.