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.