A case of hereditary diffuse leukoencephalopathy with axonal spheroids caused by a de novo mutation in CSF1R masquerading as primary progressive multiple sclerosis

Mult Scler. 2013 Sep;19(10):1367-70. doi: 10.1177/1352458513489854. Epub 2013 May 22.

Abstract

We report a sporadic case of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) confirmed by biopsy and colony-stimulating factor 1 receptor (CSF1R) sequencing. A 28-year-old woman developed progressive spastic gait and dysarthria. Brain T2/FLAIR-weighted magnetic resonance imaging showed bilateral high signal intensity lesions in the parietal deep white matter, which subsequently extended anteriorly. Biopsied brain specimens demonstrated demyelinated white matter tissue with axonal spheroids infiltrated with foamy macrophages, and CD8(+) and CD4(+) T cells. She had a heterozygous mutation, c.2381T>C (p.782 Ile>Thr), in CSF1R. This is the first genetically proven case of HDLS mimicking primary progressive multiple sclerosis.

Keywords: CSF1R; Leukoencephalopathy; T cell; demyelination; microglia; multiple sclerosis; spheroid.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Diagnosis, Differential*
  • Female
  • Humans
  • Leukoencephalopathies / diagnosis
  • Leukoencephalopathies / genetics
  • Molecular Sequence Data
  • Multiple Sclerosis, Chronic Progressive / diagnosis*
  • Mutation*
  • Receptor, Macrophage Colony-Stimulating Factor / genetics*

Substances

  • Receptor, Macrophage Colony-Stimulating Factor

Supplementary concepts

  • Hereditary Diffuse Leukoencephalopathy with Spheroids