X-Linked Adrenoleukodystrophy Screening in Newborn Males

描述（由申请人提供）：x连锁肾上腺脑白质营养不良是一种神经退行性疾病，其特征是儿童期突然发作的侵袭性大脑形式和主要表现为远端轴突病的轻度成人形式。这两种形式的主要遗传缺陷是相同的，男性患病的比例为1:21 000。所有患有这种疾病的患者都有高水平的长链脂肪酸。本研究的目的是开发一种新生儿筛查方法来检测这种疾病。患者的早期识别将使他们能够得到治疗，并使患有严重大脑形式的患者能够避免它或延缓其进展。由于总甚长链脂肪酸分析存在固有的污染问题，因此本研究将采用一种新的方法来测定鞘磷脂中脂肪酸的变化。第一个目标将集中在开发和优化鞘磷脂串联质谱分析。第二个目标是将其应用于全血样本。最后，最后一个目标是将正常人与x连锁肾上腺脑白质营养不良患者区分开来。提出的从大型脂质池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.