EFFECT OF GLYCEROL TRIERUCATE ON CLINICAL COURSE OF ADRENOLEUKODYSTROPHY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肾上腺脑白质营养不良(ALD)是一种由ABCD1基因缺陷引起的X连锁疾病，ABCD1基因是ATP结合盒转运蛋白家族的成员之一，是一种过氧体膜蛋白。ALD与组织和血浆中饱和的超长链脂肪酸(VLCFA)，特别是十六烷酸(C26：0)的积累有关。这一异常提供了诊断化验，这对受影响的男性非常敏感。ALD的发病率估计为1：17,000。虽然ALD的发病机制尚不完全清楚，但VLCFA过量很可能与疾病的表现有关。虽然VLCFA在所有组织中都有增加，但VLCFA和病理的主要积聚发生在神经系统和肾上腺皮质。 最近，洛伦佐的油治疗在减少儿童脑型疾病的发生率方面表现出了希望。我们正在一项公开试验中继续治疗，使用核磁共振成像和神经心理测试作为结果的衡量标准。 在基线评估中，年龄在18个月到6岁之间、核磁共振正常的男孩。这项研究得到了约翰·霍普金斯医院综合临床研究部的支持。男童被送入儿科临床研究单位(PCRU)，接受神经学评估、神经心理测试、营养咨询、基线血液检查、核磁共振和磁共振波谱成像(MRSI)。然后，男孩们开始接受低脂肪饮食和洛伦佐精油的治疗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adrenoleukodystrophy (ALD) is an X-linked disorder caused by defects of the ABCD1 gene, a peroxisomal membrane protein that is a member of the ATP binding cassette transporter protein family. ALD is associated with the accumulation of saturated very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C26:0) in tissues and plasma. This abnormality provides for the diagnostic assay which is exquisitely sensitive in affected males. Incidence of ALD is estimated to be 1:17,000. While the pathogenesis of ALD is incompletely understood, it is very likely that the VLCFA excess contributes to the manifestations of disease. While there is increase in all tissues, the major accumulations of VLCFA and pathology occur in the nervous system and adrenal cortex. Treatment with Lorenzo's oil has recently demonstrated promise in reducing the incidence of the childhood cerebral form of the disorder. We are continuing the treatment in an open trial using MRI and neuropsychological testing as a measure of outcome. Boys between the ages of 18 months and 6 years of age with a normal MRI at baseline assessment. This study is supported by the General Clinical Research Unit at Johns Hopkins Hospital. Boys are admitted to the Pediatric Clinical Research Unit (PCRU) and undergo neurologic assessment, neuropsychological testing, nutritional consultation, baseline blood work, and MRI and magnetic resonance spectroscopy imaging (MRSI). Boys are then begun on treatment with a diet low in fat and with Lorenzo's oil.