A rare case of late adult-onset leukodystrophy due to CSF1R mutation

The debilitating autosomal dominant inherited white matter illness known as CSF1R-related disorder (CSF1R-RD) is marked by a variety of symptoms, including cognitive impairment, neuropsychiatric abnormalities, and motor symptoms such as ataxia, seizures, and pyramidal and extrapyramidal signs. Previously, CSF1R-RD was known as adult-onset leukoencephalopathy with pigmented glia and axonal spheroids. We report a case of a 31-year-old previously healthy female who presented with progressive slowness of activities, cognitive decline, behavioral changes, speech disturbances, and motor deficits over 18 months. The illness began insidiously with bradykinesia, executive dysfunction, and inappropriate emotional responses, later evolving to spasticity, aphasia, pseudobulbar affect, urinary and fecal incontinence, and dystonia of the right upper limb. Neurological examination revealed spastic dysarthria, global cognitive impairment (MoCA score: 6), spastic quadriparesis (right > left), exaggerated reflexes, and right upper limb dystonia. MRI brain showed symmetrical T2/FLAIR hyperintensities with diffusion restriction in the periventricular white matter of the frontal and parietal lobes, along with corpus callosal atrophy. Extensive metabolic, infectious, autoimmune, and demyelinating workup was unremarkable. Whole-exome sequencing identified a pathogenic mutation in the CSF1R gene, confirming the diagnosis of adult-onset leukodystrophy with CSF1R mutation (ALSP). This case highlights the diagnostic challenges in adult-onset leukodystrophies due to their heterogeneous presentations. Recognition of characteristic neuroimaging findings and early genetic testing are pivotal for accurate diagnosis, particularly in rapidly progressive neurodegenerative disorders. This case underscores the importance of considering CSF1R-related leukoencephalopathy in young adults with cognitive decline, motor dysfunction, and distinctive MRI features.