Newborn Screening for Adrenoleukodystrophy

新生儿肾上腺脑白质营养不良筛查

• 批准号: 8063663
• 负责人: Gerald V. Raymond
• 金额: $ 29.4万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063663
• 关键词: Addison' s disease; Adrenal Glands; Adrenal gland hypofunction; Adrenoleukodystrophy; Adult; Affect; Age; Biochemical; Biological Assay; Blood; Blood specimen; Brain; Cerebrum; Cessation of life; Child; Childhood; Choline; Cystic Fibrosis; Demyelinations; Detection; Development; Diagnosis; Diet; Disease; Early Diagnosis; Early treatment; Evaluation; Family; Genes; Genetic Medicine; Health; Hematopoietic stem cells; Incidence; Individual; Inflammatory; Intervention; Investigational Therapies; Life; Link; Liquid Chromatography; Lorenzo' s oil; Lysophospholipids; Lysosomal Storage Diseases; Maryland; Masks; Mass Spectrum Analysis; Metabolic; Metabolic Brain Diseases; Metabolic Diseases; Metabolic Pathway; Methodology; Methods; Monitor; Mutation; Neonatal; Neonatal Screening; Neurologic Manifestations; Newborn Infant; Onset of illness; Organelles; Paper; Pathway interactions; Peroxisomal Disorders; Phase; Population; Public Health; Role; Sampling; Screening procedure; Sensitivity and Specificity; Sickle Cell Anemia; Spastic Paraparesis; Specificity; Spottings; Symptoms; Techniques; Therapeutic Intervention; Translations; Very Long Chain Fatty Acid; boys; design; disability; long chain fatty acid; male; oxidation; programs; stem cell therapy; tandem mass spectrometry

DESCRIPTION (provided by applicant): Adrenoleukodystropy is an X-linked disorder that has variable manifestations including adrenal insufficiency, inflammatory demyelination of the brain, and in adults, a progressive spastic paraparesis. Interventions when begun prior to disease onset can be life saving and include monitoring for adrenal and cerebral disease; early, appropriate use of hematopoietic stem cell therapy; and experimental therapy with diet and Lorenzo's oil to reduce the incidence of childhood cerebral disease. Using the biochemical abnormality of elevated very long chain fatty acids, we have recently developed a tandem mass spectrometry methodology that can detect altered elevations in lysophospholipids. This methodology is adaptable to regional newborn screening of metabolic disorders offering early diagnosis and intervention in adrenoleukodystrophy and other peroxisomal disorders. In this proposal, we propose three aims to be completed in three years. We will optimize the methodology for adaptation to large-scale screening, confirm the sensitivity of the assay in 500 newborn blood samples with a known percentage of affected individuals, and the third phase is to complete an initial field trial in Maryland of 5000 samples to confirm the sensitivity and specificity. Successful completion of the three aims would establish this as a viable addition to newborn screening. PUBLIC HEALTH RELEVANCE: The public health importance of this proposal is that adrenoleukodystrophy is a serious disorder affecting children and adults with an incidence of approximately 1:20,000. Therapies, which have been developed, rely extensively on presymptomatic diagnosis and monitoring which unfortunately occurs in only a limited percentage of individuals. We propose to develop a methodology which can occur with standard regional newborn screening and confirm the sensitivity and specificity of the technique. Broader use of this optimized method should allow quicker diagnosis for families and maximum translation of recent therapeutic interventions.

描述（由申请人提供）：肾上腺肾上腺素是一种X连锁疾病，具有可变的表现，包括肾上腺功能不全，大脑的炎性脱髓鞘以及成人，一种进行性痉挛性痉挛。在疾病发作之前开始的干预措施可以是挽救生命的，包括监测肾上腺和脑疾病；早期，适当使用造血干细胞疗法；以及饮食和洛伦佐（Lorenzo）油的实验疗法，以减少儿童脑疾病的发生率。使用升高的非常长的链脂肪酸的生化异常，我们最近开发了一种串联质谱法，可以检测到溶物磷脂中升高的改变。该方法可适应新生儿筛查的代谢疾病，可早期诊断和干预肾上腺素疾病和其他过氧化物酶体疾病。在此提案中，我们建议三年内完成三个目标。我们将优化适应大规模筛查的方法，确认该测定法对500个新生儿样本中具有已知百分比的受影响个体的敏感性，第三阶段是在马里兰州完成5000个样本的初步现场试验以确认敏感性和特异性。这三个目标的成功完成将确定这是对新生儿筛查的可行补充。公共卫生相关性：该提案的公共卫生重要性是，肾上腺素肌营养不良是一种严重的疾病，影响儿童和成人，发生率约为1：20,000。已经开发的疗法广泛依赖于预症状诊断和监测，不幸的是，仅在有限的个体中发生。我们建议开发一种可以通过标准的区域新生儿筛查进行的方法，并确认技术的敏感性和特异性。这种优化方法的更广泛使用应可以更快地诊断家庭，并最大程度地翻译最近的治疗干预措施。

项目成果

Newborn screening for X-linked adrenoleukodystrophy: further evidence high throughput screening is feasible.

• DOI: 10.1016/j.ymgme.2013.10.019
• 发表时间: 2014-01
• 期刊: MOLECULAR GENETICS AND METABOLISM
• 影响因子: 3.8
• 作者: Theda, Christiane;Gibbons, Katy;DeFor, Todd E.;Donohue, Pamela K.;Golden, W. Christopher;Kline, Antonie D.;Gulamali-Majid, Fizza;Panny, Susan R.;Hubbard, Walter C.;Jones, Richard O.;Liu, Anita K.;Moser, Ann B.;Raymond, Gerald V.
• 通讯作者: Raymond, Gerald V.

Newborn screening for adrenoleukodystrophy: implications for therapy.

新生儿肾上腺脑白质营养不良筛查：对治疗的影响。

• DOI: 10.1007/bf03256261
• 发表时间: 2007
• 期刊: Molecular diagnosis & therapy
• 影响因子: 4
• 作者: Raymond,GeraldV;Jones,RichardO;Moser,AnnB
• 通讯作者: Moser,AnnB