Work

Neuropathologic Features of Adult-Onset Progressive Leukodystrophy Due to KARS Pathogenic Variants

Year: 2026

Type: article

Abstract: Objectives: and expand on neuroradiologic features reported in other cases. Methods: We present the clinical, neuroimaging, and histopathologic findings of a patient with adult-onset, rapidly progressive leukodystrophy. Clinical information, genetic reports, neuroimaging, and postmortem brain pathology were collected and analyzed. Results: were found, including the previously reported (NM_001130089.1: c.683 C > T, p.P228L) pathogenic variant and a novel (NM_001130089.1: c.1609 C > T, p.R537W) variant of uncertain significance (VUS). Brain MRI revealed extensive, frontally predominant white matter abnormalities, involvement of the corticospinal tracts extending into the midbrain, and nodular contrast enhancement primarily in the bilateral occipital cortices and leptomeninges, noncontiguous with the white matter lesions. Autopsy 1 year later revealed frontally predominant atrophy of the white matter with relative preservation of the subcortical U-fibers, brainstem, and cerebellum; microcytic parenchymal degeneration and vacuolization; and numerous axonal spheroids. No inflammatory component was present in the occipital cortex or leptomeninges. Discussion: Our findings confirm the previously reported features of DEAPLE and suggest the possibility of a transient neuroinflammatory component associated with areas of active disease.

Source: Neurology Genetics

DOI: 10.1212/nxg.0000000000200419

Authors: Amanda Nagy, Michael S. Marshall, Matthew P. Frosch, Yedda Li, Melissa A. Walker, Florian S. Eichler

Institution: Massachusetts General Hospital

Language: English

Topic: Hereditary Neurological Disorders

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,300