The latest on leukodystrophies
The latest on leukodystrophies
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DOI：
10.1097/00019052-200404000-00017
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发表时间：
2004-04-01
影响因子：
4.8
通讯作者：
van der Knaap, MS
中科院分区：
文献类型：
--
作者：
Schiffmann, R;van der Knaap, MS
综述目的 我们对白质遗传性疾病的理解已经取得了重要进展，并在此进行讨论。 最新发现 最近发现，编码真核细胞起始因子 2B (eIF2B) 五个亚基的基因突变是白质消失性疾病/儿童共济失调伴中枢性髓鞘形成不足综合征的原因。讨论了 eIF2B 相关疾病的临床特征扩展到婴儿和成人发病的疾病。描述了新的临床影像综合征，例如伴有基底节和小脑萎缩的髓鞘形成不足以及伴有脑干和脊髓受累的白质脑病以及白质乳酸升高。最近的发现包括证据表明线粒体脂肪氧化异常可能在肾上腺脑白质营养不良的发病机制中很重要，并且突变的髓磷脂蛋白可导致其他髓磷脂蛋白分布不良，从而导致髓鞘形成障碍、轴突损伤或两者兼而有之。 eIF2B 相关疾病的临床谱包括从严重的、快速进展的先天性或早期婴儿脑病到通常与卵巢早衰相关的缓慢进展的认知和运动退化。描述了两种新认识的脑白质营养不良综合征：髓鞘形成不足伴基底神经节和小脑萎缩，以及白质脑病伴脑干和脊髓受累以及白质乳酸升高。还提供了肾上腺脑白质营养不良和髓磷脂蛋白相关疾病的更新。本次更新表明，越来越多的遗传缺陷正在被发现，这些缺陷可能导致原发性白质疾病。
Purpose of review Important advances in our understanding of genetic disorders of the white matter have been made and are discussed here.Recent findings It has recently been discovered that mutations in the genes encoding the five subunits of eukaryocytic initiation factor 2B (eIF2B) are the cause of vanishing white-matter disease/ childhood ataxia with central hypomyelination syndrome. The extension of the clinical features of the eIF2B-related disorders to encompass both infant- and adult-onset disorders is discussed. New clinico-imaging syndromes such as hypomyelination with atrophy of the basal ganglia and cerebellum and leukoencephalopathy with brain-stem and spinal cord involvement and elevated white-matter lactate are described. Recent findings include evidence that mitochondrial fat-oxidation abnormalities may be important in the pathogenesis of adrenoleukodystrophy, and that a mutant myelin protein can cause maldistribution of other myelin proteins, causing dysmyelination, axonal damage, or both.Summary This review focuses on advances in the understanding of the role of eIF2B as a cause of a common leukodystrophy syndrome. eIF2B-related disorders have a clinical spectrum ranging from a severe, rapidly progressive congenital or early infantile encephalopathy to a slowly progressive cognitive and motor deterioration often associated with premature ovarian failure. Two newly recognized leukodystrophy syndromes are described: hypomyelination with atrophy of the basal ganglia and cerebellum, and leukoencephalopathy with brain-stem and spinal cord involvement and elevated white-matter lactate. An update is also given for adrenoleukodystrophy and myelin-protein-related disorders. This update demonstrates that an increasing number of genetic defects are being identified that may cause primary white-matter disorders.