EFFECT OF GLYCEROL TRIERUCATE ON CLINICAL COURSE OF ADRENOLEUKODYSTROPHY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 肾上腺脑白质营养不良（ALD）是由ABCD 1基因缺陷引起的X-连锁疾病，ABCD 1基因是ATP结合盒转运蛋白家族的一个成员的过氧化物酶体膜蛋白。ALD与组织和血浆中饱和极长链脂肪酸（VLCFA），特别是二十六烷酸（C26：0）的积累相关。这种异常提供了在受影响的男性中非常敏感的诊断测定。ALD的发病率估计为1：17，000。虽然ALD的发病机制还不完全清楚，但很可能是VLCFA过量导致了疾病的表现。虽然在所有组织中均有增加，但VLCFA的主要蓄积和病理发生在神经系统和肾上腺皮质。 最近，用洛伦佐油治疗已经证明有希望减少儿童大脑形式的疾病的发生率。我们正在继续进行一项开放试验，使用MRI和神经心理学测试作为结果的衡量标准。 基线评估时MRI正常的18个月至6岁男孩。本研究由约翰霍普金斯医院的一般临床研究单位支持。男孩被送往儿科临床研究单位（PCRU），并接受神经系统评估，神经心理测试，营养咨询，基线血液工作，MRI和磁共振波谱成像（MRSI）。然后男孩开始接受低脂肪饮食和洛伦佐油的治疗。

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.