X-Linked Adrenoleukodystrophy Screening in Newborn Males

新生儿男性 X 连锁肾上腺脑白质营养不良筛查

• 批准号: 6550129
• 负责人: EDWIN W NAYLOR
• 金额: $ 9.85万
• 依托单位: PEDIATRIX SCREENING, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6550129
• 关键词: adrenoleukodystrophy; blood chemistry; diagnosis design /evaluation; diagnosis quality /standard; diagnostic tests; early diagnosis; electrospray ionization mass spectrometry; genetic disorder diagnosis; genetic screening; long chain fatty acid; male; newborn human (0-6 weeks); sex linked trait; sphingomyelins; technology /technique development

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.

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，其特征为在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较温和的成人形式。主要的遗传缺陷在两种形式中是相同的，其频率为1：21，000男性。所有患有这种疾病的患者都有极长链脂肪酸水平升高。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。早期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迟其进展。由于总的极长链脂肪酸分析有固有的污染问题，本研究将采取新的方法，确定脂肪酸的变化，在一个脂质馏分，鞘磷脂。第一个目标将集中于开发和优化鞘磷脂的串联质谱分析。第二个目标将集中在其应用于全血样本。最后，最后一个目标将旨在区分正常个体与X连锁肾上腺脑白质营养不良患者。所提出的从大脂质池中取样的方法代表了研究疾病的新手段。