Kim Jae Rim, Lee Suin, Seo Sang Won, Jang Ja-Hyun, Suh Yeon Lim, Park Jeong Ho, Lee Seung-Yeon, Son Hyo Jin, Kwon Hee Jung, Kim Eun-Joo, Na Duk L, Jang Hyemin, Kim Hee Jin
Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
Department of Neurology, Neuroscience Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.
Sci Rep. 2025 Jan 13;15(1):1857. doi: 10.1038/s41598-024-84665-w.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter disease characterized by axonal and glial injury. Although its clinical characteristics have been described in case reports, the prevalence of CSF1R mutations in clinically suspected ALSP cases remains unclear. Herein, we analysed the frequency of CSF1R mutations in patients with probable or possible ALSP and describe the genetic, clinical, radiological, and pathological findings of ALSP cases in individuals of Korean ancestry. Twenty-eight patients with probable or possible ALSP diagnosed at Samsung Medical Center, Seoul, between January 2014 and August 2020, were retrospectively reviewed. All participants underwent brain magnetic resonance imaging (MRI) and CSF1R genetic testing. Overall, 9 of the 28 patients (32.1%) [5/6 (83.3%) of probable ALSP and 4/22 (18.2%) of possible ALSP] were confirmed to have pathogenic or likely pathogenic variants in CSF1R gene. Additionally, one patient without CSF1R mutation exhibited histopathological findings consistent with ALSP on brain biopsy. All patients with CSF1R mutation presented with cognitive impairment and/or psychiatric symptoms. Brain MRI revealed bilateral white matter hyperintensities in all patients, and 5/8 (62.5%) showed diffusion-restricted lesions. Notably, patients with CSF1R mutation had younger age at onset, rapidly progressive course, and diffuse hyperintensity in the splenium compared to patients without CSF1R mutation. Our findings suggest that for definite diagnosis, CSF1R genetic testing is recommended in patients who meet the diagnostic criteria for possible or probable ALSP. Our findings provide insights into the genetic, clinical, radiological, and pathological dimensions of ALSP in individuals of Korean ancestry.
成人起病的轴突球状体和色素性神经胶质细胞性白质脑病(ALSP)是一种罕见的白质疾病,其特征为轴突和神经胶质损伤。尽管病例报告中已描述了其临床特征,但临床疑似ALSP病例中CSF1R突变的患病率仍不清楚。在此,我们分析了可能或疑似ALSP患者中CSF1R突变的频率,并描述了韩国血统个体中ALSP病例的遗传、临床、放射学和病理学发现。回顾性分析了2014年1月至2020年8月在首尔三星医疗中心诊断为可能或疑似ALSP的28例患者。所有参与者均接受了脑磁共振成像(MRI)和CSF1R基因检测。总体而言,28例患者中有9例(32.1%)[可能的ALSP患者中5/6(83.3%),可能的ALSP患者中4/22(18.2%)]被证实CSF1R基因存在致病性或可能致病性变异。此外,1例无CSF1R突变的患者在脑活检时表现出与ALSP一致的组织病理学发现。所有CSF1R突变患者均出现认知障碍和/或精神症状。脑MRI显示所有患者双侧白质高信号,5/8(62.5%)显示扩散受限病变。值得注意的是,与无CSF1R突变的患者相比,CSF1R突变患者发病年龄更小,病程进展迅速,胼胝体弥漫性高信号。我们的研究结果表明,对于明确诊断,建议对符合可能或疑似ALSP诊断标准的患者进行CSF1R基因检测。我们的研究结果为韩国血统个体中ALSP的遗传、临床、放射学和病理学方面提供了见解。