Clin Neuropathol. 2022 Sep-Oct;41(5):219-225. doi: 10.5414/NP301459.
Amyotrophic lateral sclerosis (ALS) is a disorder with strong clinical and genetic heterogeneity, and its pathogenic mechanism has not been completely clarified. Proximal myopathy is rare in clinical manifestations of ALS. Here, we describe a 34-year-old woman with a 1-year history of symmetrical, proximal limb weakness, and muscle atrophy, with slow progression and no upper motor neuron (UMN) signs. The clinical phenotype was similar to myopathy and was initially misdiagnosed as proximal myopathy. Electromyography (EMG) and muscle and nerve biopsy were performed. The genomic DNA from the patient's peripheral blood lymphocytes was analyzed. The EMG and pathologic examinations revealed chronic neurogenic changes and mild mixed peripheral neuropathy. DNA analysis revealed a heterozygous missense mutation in exon 1 at codon 50 (c.50>C) of , and a heterozygous missense mutation in exon 11 at codon 1013 (c.1013G>A) of that has not been reported previously. The patient was diagnosed as familial ALS (FALS) type 1, and the patient had a family history of autosomal dominant (AD) pattern. This report expands the knowledge of the clinical phenotype of FALS. For patients with clinical manifestations mimicking proximal myopathy, the possibility of underlying ALS should be considered.
肌萎缩侧索硬化症（ALS）是一种具有强烈临床和遗传异质性的疾病，其发病机制尚未完全阐明。近端肌病在 ALS 的临床表现中较为罕见。在这里，我们描述了一位 34 岁女性，其病史为 1 年的对称性、近端肢体无力和肌肉萎缩，进展缓慢，无运动神经元（UMN）征。临床表型类似于肌病，最初被误诊为近端肌病。进行了肌电图（EMG）和肌肉及神经活检。分析了患者外周血淋巴细胞的基因组 DNA。EMG 和病理检查显示慢性神经源性改变和轻度混合性周围神经病。DNA 分析显示在 外显子 1 第 50 密码子（c.50>C）处存在杂合错义突变，以及在 外显子 11 第 1013 密码子（c.1013G>A）处存在杂合错义突变，这些突变此前尚未报道过。患者被诊断为 1 型家族性 ALS（FALS），且患者具有常染色体显性（AD）遗传模式的家族史。本报告扩展了 FALS 的临床表型知识。对于临床表现类似于近端肌病的患者，应考虑潜在的 ALS 可能性。
