X-Linked Adrenoleukodystrophy Screening in Newborn Males

描述(申请人提供)：X连锁肾上腺脑白质营养不良是一种神经退行性疾病，其特征是在儿童时期突然发作的侵袭性脑形式和主要表现为远端轴索病变的较轻的成人形式。原发遗传缺陷在两种形式中都是相同的，其频率为1：21,000男性。所有患有这种疾病的患者都有超长链脂肪酸水平的升高。这项研究的目的是建立一种新生儿筛查方法来检测这种疾病。及早识别患者将使他们能够得到治疗，并使患有严重脑型的患者能够避免或延缓其进展。由于总超长链脂肪酸分析存在固有的污染问题，本研究将采用一种新的方法来确定脂肪组份-鞘磷脂中的脂肪酸变化。第一个目标将集中在开发和优化一种鞘磷脂的串联质谱分析方法。第二个目标是将其应用于全血样本。最后，最后一个目标是区分正常个体和X连锁肾上腺脑白质营养不良患者。所提出的从大量脂类中取样的方法代表了一种研究疾病的新手段。

DESCRIPTION (provided by applicant): X-linked adrenoleukodystrophy is a neurodegenerative disorder that is characterized by both an aggressive cerebral form that suddenly strikes in childhood and by a milder adult form that presents primarily as a distal axonopathy. The primary genetic defect is identical in both forms and it has a frequency of 1:21,000 males. All patients with the disorder have elevated levels of levels of very long chain fatty acids. The purpose of this study is to develop a newborn screening assay to detect the disorder. Early identification of the patients will allow them to be treated and will enable patients with the severe cerebral form to either avoid it or delay its progression. Because total very long chain fatty acid analysis has inherent contamination problems, this study will take the novel approach of determining fatty acid changes in one lipid fraction, sphingomyelin. The first aim will focus on developing and optimizing a tandem mass spectrometry assay for sphingomyelins. The second aim will focus on its application to whole blood samples. Finally, the last aim will aim at differentiating normal individuals from X-linked adrenoleukodystrophy patients. The proposed approach of sampling from a large lipid pool represents a new means to study diseases.