title: Dysmyelination revisited.
abstract: Dysmyelination describes an inborn error of metabolism affecting myelinogenesis that causes it to be abnormal, arrested, or delayed. Abiotrophy or myelin as defined by Gowers, due to metabolic failure of the myelin maintenance system, is yet another feature of dysmyelination. In addition to the leukodystrophies, genetically determined conditions such as infantile amaurotic idiocy, hematosidosis, Niemann-Pick's disease and several of the aminoacidopathies are examples of dysmyelinating diseases. In order to reconcile morphological and neurochemical data in these conditions, it is necessary to reexamine a number of pathogenetic hypotheses based on known enzymatic deficiencies, and the interpretation of fragmentary biochemical analyses. The obligatory role of the neuron and axon in myelin formation and maintenance is reviewed. The hypothesis is advanced that gangliosides and their degradative products constitue precursors for the synthesis of the characteristic myelin sphingolipids cerebrosides, sulfatides, and sphingomyelin. Alterations in axoplasmic flow and of ganglioside metabolism must be condidered as important factors in the pathogenesis of dysmyelination.
mesh_terms: D001369:Axons / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism; D002554:Cerebrosides / Q000096:biosynthesis; D005696:Galactosidases / Q000172:deficiency; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000378:metabolism; D007966:Leukodystrophy, Metachromatic / Q000378:metabolism; D008064:Lipidoses / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000378:metabolism
chemical_list: D002554:Cerebrosides; D005732:Gangliosides; D013433:Sulfoglycosphingolipids; D005696:Galactosidases