Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Associated with the CSF1R p. (Ile843Thr) Variant: Clinical, Imaging, and Molecular Characterization
Abstract
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a microgliopathy caused by pathogenic CSF1R variants. We report the first Japanese case of ALSP harboring the CSF1R p. (Ile843Thr) variant. The patient presented with progressive cognitive and behavioral decline followed by motor dysfunction, and MRI showed frontoparietal-predominant white matter lesions and corpus callosum thinning. A functional analysis demonstrated impaired autophosphorylation of the mutant protein, confirming pathogenicity. This case expands the CSF1R variants spectrum of ALSP and highlights the diagnostic value of integrating genetic testing with functional validation in adult-onset leukoencephalopathies, even when family history is absent.
Related
- Pigmented purpura dermatosis associated with compounded semaglutide: A case report and literature review of medication-associated pigmented purpuric dermatosis
- Characterization of 3D heterocellular spheroids of pancreatic ductal adenocarcinoma for the study of cell interactions in the tumor immune microenvironment
- Pigmented Orocutaneous Fistula: A Diagnostic Dilemma Unmasked by Dermoscopy.
- Pigmented Purpura of Doucas and Kapetanakis in Pediatric Patients: A Rare Report of Six Cases.
- Characteristics of progressive multifocal leukoencephalopathy in hematological malignancies, With reference to HIV-infected patients
BibTeX
@article{mima2026adultonset,
title = {{Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Associated with the CSF1R p. (Ile843Thr) Variant: Clinical, Imaging, and Molecular Characterization}},
author = {Yohei Mima and Hisakazu Nakajima and Masataka Koike and Toshiaki Goda and Sae Mizuno and Toshiya Kizaki and Norikazu Hara and Takeshi Ikeuchi},
journal = {Internal Medicine},
year = {2026},
month = oct,
doi = {10.2169/internalmedicine.6854-25},
url = {https://www.jstage.jst.go.jp/article/internalmedicine/65/19/65_6854-25/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Associated with the CSF1R p. (Ile843Thr) Variant: Clinical, Imaging, and Molecular Characterization
AU - Yohei Mima
AU - Hisakazu Nakajima
AU - Masataka Koike
AU - Toshiaki Goda
AU - Sae Mizuno
AU - Toshiya Kizaki
AU - Norikazu Hara
AU - Takeshi Ikeuchi
PY - 2026
DA - 2026/10/01
JO - Internal Medicine
DO - 10.2169/internalmedicine.6854-25
UR - https://www.jstage.jst.go.jp/article/internalmedicine/65/19/65_6854-25/_article
AB - Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a microgliopathy caused by pathogenic CSF1R variants. We report the first Japanese case of ALSP harboring the CSF1R p. (Ile843Thr) variant. The patient presented with progressive cognitive and behavioral decline followed by motor dysfunction, and MRI showed frontoparietal-predominant white matter lesions and corpus callosum thinning. A functional analysis demonstrated impaired autophosphorylation of the mutant protein, confirming pathogenicity. This case expands the CSF1R variants spectrum of ALSP and highlights the diagnostic value of integrating genetic testing with functional validation in adult-onset leukoencephalopathies, even when family history is absent.
SN - 1349-7235
SN - 0918-2918
ER -