Abstract
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.