Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Leukodystrophies — much more than just diseases of myelin

Nature Reviews Neurology volume 14, pages 747–748 (2018)Cite this article

Subjects

A Review article in the February 2018 issue of Nature Reviews Neurology (Adult leukodystrophies. Nat. Rev. Neurol. 14, 94–105; 2018)1 highlights adult presentations of leukodystrophies. This is an important topic, as leukodystrophies are commonly associated with childhood, and adult neurologists may be undereducated on the subject1. The paper starts with a broad definition of leukodystrophies as inherited disorders that affect the white matter of the CNS; cells involved in the axon–glia unit, including oligodendrocytes, astrocytes, ependymal cells and microglia, are specifically affected. The authors explain that underlying pathological mechanisms vary widely, and that in many cases pathological assessment is not feasible because of lack of brain tissue, so clinicians must rely on the molecular aetiology of the disorder and the appearance of the white matter on neuroimaging to define and classify the various disorders.

Surprisingly, the authors then classify leukodystrophies into only two categories: hypomyelinating leukodystrophies, which are primary deficits in myelin development, and demyelinating leukodystrophies, where myelin develops normally but subsequently undergoes progressive disruption. The Review is built on this concept1.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Multifaceted neuropathology of leukodystrophies.
The alternative text for this image may have been generated using AI.

References

  1. Köhler, W., Curiel, J. & Vanderver, A. Adulthood leukodystrophies. Nat. Rev. Neurol. 14, 94–105 (2018).

    Article  Google Scholar 

  2. Vanderver, A. et al. Case definition and classification of leukodystrophies and leukoencephalopathies. Mol. Genet. Metab. 114, 494–500 (2015).

    Article  CAS  Google Scholar 

  3. van der Knaap, M. S. et al. Megalencephalic leukoencephalopathy with cysts without MLC1 defect. Ann. Neurol. 67, 834–837 (2010).

    PubMed  Google Scholar 

  4. López-Hernández, T. et al. Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. Am. J. Hum. Genet. 88, 422–432 (2011).

    Article  Google Scholar 

  5. Steenweg, M. E. et al. Leukoencephalopathy with thalamus and brainstem involvement and high lactate ‘LTBL’ caused by EARS2 mutations. Brain 135, 1387–1394 (2012).

    Article  Google Scholar 

  6. van der Knaap, M. S. & Bugiani, M. Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol. 134, 351–382 (2017).

    Article  Google Scholar 

  7. Rademakers, R. et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat. Genet. 44, 200–205 (2012).

    Article  CAS  Google Scholar 

  8. Bugiani, M. et al. Leukoencephalopathy with vanishing white matter: a review. J. Neuropathol. Exp. Neurol. 69, 987–996 (2010).

    Article  Google Scholar 

  9. Duncan, I. D. & Radcliff, A. B. Inherited and acquired disorders of myelin: the underlying myelin pathology. Exp. Neurol. 283, 452–475 (2016).

    Article  CAS  Google Scholar 

  10. van der Knaap, M. S. et al. Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course. Acta Neuropathol. 92, 206–212 (1996).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Child Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands

    Marjo S. van der Knaap

  2. Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam Neuroscience, Amsterdam, Netherlands

    Marjo S. van der Knaap

  3. Department of Neuropathology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands

    Marianna Bugiani

Authors
  1. Marjo S. van der Knaap
    View author publications

    Search author on:PubMed Google Scholar

  2. Marianna Bugiani
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Marjo S. van der Knaap.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van der Knaap, M.S., Bugiani, M. Leukodystrophies — much more than just diseases of myelin. Nat Rev Neurol 14, 747–748 (2018). https://doi.org/10.1038/s41582-018-0093-9

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41582-018-0093-9

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing