title: Some thoughts on the neurobiology of the leukodystrophies.
abstract: The known leukodystrophies are genetic diseases involving defects in oligodendroglial function and myelinogenesis. The various steps in the process of myelination and myelin maintenance are outlined beginning with gliogenesis and ending with myelin catabolism. A gene defect affecting any one of these steps has the potential to lead either to a leukodystrophy or to a more systemic disease. The shiverer mouse mutant involves deletion of the gene for basic protein, and the quaking mutant may involve defective myelin assembly. Zellweger's syndrome, a systemic human disease, has a severe deficiency of plasmalogens, which are major myelin lipids. This deficiency is presumably a consequence of absent peroxisomes, organelles that contain the essential synthetic enzymes for these lipids. The three human leukodystrophies for which metabolic lesions are known (metachromatic leukodystrophy, globoid cell leukodystrophy and adrenoleukodystrophy), however, all have deficits in the very end stage of myelinogenesis, that of catabolism of myelin lipids. Is this coincidence? Perhaps some of the undiagnosed neurological diseases of children, as well as known diseases with unknown genetic defects, involve deletions or mutations in genes controlling earlier stages of myelinogenesis.
mesh_terms: D000326:Adrenoleukodystrophy / Q000503:physiopathology*; D001253:Astrocytes / Q000502:physiology; D001369:Axons / Q000502:physiology; D002648:Child; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000503:physiopathology*; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000503:physiopathology*; D007966:Leukodystrophy, Metachromatic / Q000503:physiopathology*; D050356:Lipid Metabolism; D008830:Microbodies / Q000502:physiology; D009185:Myelin Proteins / Q000502:physiology; D009186:Myelin Sheath / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D004798:Enzymes; D009185:Myelin Proteins