Abstract
Abnormalities of myelin are common in lysosomal and peroxisomal disorders. Most display a primary loss of myelin in which the myelin sheath and/or oligodendrocytes are selectively targeted by diverse pathogenetic processes. The most severe and, hence, clinically relevant are heritable diseases predominantly of infants and children, the leukodystrophies: metachromatic, globoid cell (Krabbe disease) and adreno-leukodystrophy. Our still limited understanding of these diseases has derived from multiple sources: originally, neurological–neuropathologic–neurochemical correlative studies of the natural disease in humans or other mammals, which has been enhanced by more sophisticated and contemporary techniques of cell and molecular biology. Transgenic mouse models seem to be the most promising methodology, allowing the examination of the cellular role of lysosomes and peroxisomes for formation and maintenance of both myelin and axons, and providing initial platforms to evaluate therapies. Treatment options are woefully inadequate and in their nascent stages, but still inspire some hope for the future.
Acknowledgements
The authors wish to thank MS van der Knaap for providing the magnetic resonance images presented in this article.
Financial & competing interests disclosure
Edward M Kaye is a full-time employee of Genzyme involved in clinical research in lysosomal storage diseases, but is not involved in any programs for the leukodystrophies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest or in financial conflict with the subject matter or materials discussed in the part from those disclosed.
No writing assistance was utilized in the production of this manuscript.