Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Associated with the CSF1R p....

Area of Science:

• Neurogenetics
• Neuropathology
• Molecular Medicine

Background:

• Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare neurological disorder characterized by microgliopathy.
• It is primarily caused by pathogenic variants in the colony-stimulating factor 1 receptor (CSF1R) gene.

Purpose of the Study:

• To report the first documented case of ALSP in a Japanese patient.
• To characterize the clinical, radiological, and genetic features of this novel case.
• To confirm the pathogenicity of a newly identified CSF1R variant.

Main Methods:

• Clinical assessment including cognitive, behavioral, and motor function evaluation.
• Magnetic Resonance Imaging (MRI) to identify white matter abnormalities.
• Genetic sequencing to identify CSF1R variants.
• Functional analysis of the identified CSF1R variant to assess protein function.

Main Results:

• The patient presented with progressive cognitive decline, behavioral changes, and motor dysfunction.
• MRI revealed frontoparietal white matter lesions and corpus callosum thinning.
• A novel CSF1R variant, p.(Ile843Thr), was identified.
• Functional studies confirmed impaired autophosphorylation of the mutant CSF1R protein, indicating pathogenicity.

Conclusions:

• This case represents the first Japanese ALSP patient with the CSF1R p.(Ile843Thr) variant, broadening the known spectrum of ALSP-associated genetic mutations.
• The findings underscore the importance of integrating genetic testing with functional validation for diagnosing adult-onset leukoencephalopathies, particularly in sporadic cases.
• This study contributes to a better understanding of ALSP pathogenesis and diagnosis.