Norton W T
Neuropediatrics. 1984 Sep;15 Suppl:28-31. doi: 10.1055/s-2008-1052379.
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.
已知的脑白质营养不良是涉及少突胶质细胞功能和髓鞘形成缺陷的遗传性疾病。从神经胶质细胞生成开始到髓鞘分解代谢结束，概述了髓鞘形成和髓鞘维持过程中的各个步骤。影响这些步骤中任何一个的基因缺陷都有可能导致脑白质营养不良或更全身性的疾病。颤抖小鼠突变体涉及碱性蛋白基因的缺失，而颤抖突变体可能涉及有缺陷的髓鞘组装。人类全身性疾病齐-韦二氏综合征存在严重的缩醛磷脂缺乏，而缩醛磷脂是主要的髓鞘脂质。这种缺乏大概是由于过氧化物酶体缺失所致，过氧化物酶体是含有这些脂质必需合成酶的细胞器。然而，已知代谢病变的三种人类脑白质营养不良（异染性脑白质营养不良、球形细胞脑白质营养不良和肾上腺脑白质营养不良），在髓鞘形成的最后阶段，即髓鞘脂质分解代谢阶段均有缺陷。这是巧合吗？也许一些未确诊的儿童神经系统疾病，以及具有未知基因缺陷的已知疾病，都涉及控制髓鞘形成早期阶段的基因缺失或突变。
