PDF(Pubmed)
Abstract：
The history of adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN) and other peroxisomal diseases is exemplary for the stunning progress of scientific medicine within the past 50 years. Like many breakthroughs in medicine, the detailed analysis of patients\' pathologically affected tissues was instrumental, resulting in stepwise systematic clarification of what had remained enigmatic until the 1970s. This flashback paper is a recollection of the first neuropathological description of a slowly evolving clinical phenotype, spastic paraparesis with adrenal insufficiency, in a young adult by Budka et al. 1976 [3], using virtual microscopy of the original histologic slides. The clinico-pathological presentation derives from the classical cerebral ALD phenotype in boys, where electron microscopy demonstrated the underlying pathological hallmark of characteristic lipid inclusions shared by both phenotypes. Our report allowed the delineation of a new disease type almost simultaneously described in more cases as AMN by Griffin et al. 1977 [4] and Schaumburg et al. 1977 [11]. Moreover, our report indicated clinical heterogeneity in the ALD disease group that, as shown later, extends further to females, to Addison-only, and even to asymptomatic subjects. The gene underlying ALD was discovered in 1993 as a defect in the ABCD1 gene. Yet, it has hitherto remained unclear how the gene defect causes the strikingly broad and unpredictable phenotypic spectrum of ALD/AMN.
摘要：
肾上腺脑白质营养不良（ALD）的历史，肾上腺脊髓神经病变（AMN）和其他过氧化物酶体疾病是过去50年来科学医学惊人进步的典范。像医学上的许多突破一样，对患者的病理影响组织的详细分析是工具性的，导致逐步系统地澄清直到20世纪70年代仍然神秘的东西。这篇倒叙论文是对缓慢发展的临床表型的第一个神经病理学描述的回忆，痉挛性轻瘫伴肾上腺功能不全，Budka等人在一个年轻的成年人中。1976年[3],使用原始组织学载玻片的虚拟显微镜。临床病理表现来自男孩的经典脑ALD表型，电子显微镜显示了两种表型共有的特征性脂质内含物的潜在病理标志。我们的报告允许对Griffin等人在更多病例中几乎同时描述为AMN的新疾病类型进行描述。1977[4]和Schaumburg等人。1977年[11]。此外，我们的报告表明ALD疾病组的临床异质性，如稍后所示，进一步延伸到女性，只有艾迪生，甚至是无症状的受试者。ALD基础基因在1993年作为ABCD1基因的缺陷被发现。然而，迄今为止，尚不清楚基因缺陷如何导致ALD/AMN的惊人的广泛和不可预测的表型谱。
