目的：报道1例携带HARS1基因变异并伴脑脊液蛋白升高的散发型肌萎缩侧索硬化症（amyotrophic lateral sclerosis，ALS）患者的临床资料，探讨ALS患者脑脊液蛋白改变的临床意义，并就本例HARS1基因变异伴脑脊液蛋白升高进行讨论。

方法：对1例ALS患者的临床表现、电生理、影像学、脑脊液及基因检测结果进行报道，并结合文献复习及分析。

结果：患者为中年女性，持续进展性病程，以肢体进行性无力为主要表现，伴构音障碍及舌肌萎缩，存在腱反射亢进及病理征阳性。脑脊液检查显示蛋白升高，肌电图提示广泛神经源性损害，影像学检查提示皮质脊髓束受累，基因检测发现HARS1 c.210G＞A （p.Met70Ile）杂合变异，临床综合诊断为ALS。经利鲁唑片、辅酶Q10及短期激素治疗后病情平稳。

结论：本例为携带罕见HARS1变异的ALS患者，提示该基因的临床表型谱可能较既往报道更为广泛。患者脑脊液蛋白轻度升高，主要反映血脑屏障功能障碍而非免疫炎症反应。HARS1变异在本例病例报道中可能具有致病、修饰或偶然携带的作用，尚需进一步功能学研究和病例积累验证。脑脊液蛋白轻度升高在ALS中并不少见，现阶段不能据此推断其与HARS1变异存在特异关联；二者可能为独立并存，或通过共同的神经退行性病理过程产生间接联系。

Objective: To report the clinical features of a sporadic amyotrophic lateral sclerosis (ALS) patient carrying a HARS1 variant with mildly elevated cerebrospinal fluid (CSF) protein, and to discuss the clinical significance of CSF protein changes in ALS as well as the co-occurrence of the HARS1 variant and CSF protein elevation.

Methods: The patient's clinical symptoms, electrophysiology, imaging, cerebrospinal fluid, and genetic test results were documented, alongside a literature review and analysis.

Results: The patient, a middle-aged female, presented with a progressively worsening disease course. The primary clinical manifestations included increasing limb weakness, dysarthria, atrophy of the tongue muscles, hyperactive tendon reflexes, and positive pathological signs. Cerebrospinal fluid analysis revealed elevated protein levels. Electromyography demonstrated extensive neurogenic damage, while imaging studies indicated involvement of the corticospinal tract. Genetic testing identified a heterozygous variant of HARS1 c.210G>A (p.Met70Ile).Based on these findings, a clinical diagnosis of ALS was established. Following treatment with riluzole, coenzyme Q10, and short-term corticosteroid therapy, the patient's condition stabilized.

Conclusion: This ALS patient with a rare HARS1 variant suggests a broader clinical spectrum for this gene than previously known. The slight increase in CSF protein indicates blood-brain barrier dysfunction rather than an immune response. The pathogenicity of the HARS1 variant needs further study and additional cases for confirmation. As mild CSF protein elevation is not uncommon in ALS, it should not be interpreted as specifically attributable to the HARS1 variant; the two findings may be independent or indirectly linked by shared neurodegenerative pathology.