Epidemiology of SBCAD Deficiency in Hmong-Americans

美洲苗族 SBCAD 缺乏症的流行病学

• 批准号: 7198166
• 负责人: Maureen S Durkin
• 金额: $ 32.07万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198166
• 关键词: Adverse event; Affect; Age; American; Archives; Behavior; Benign; Biochemical; Birth; Blood; Blood specimen; Carnitine; Case Study; Characteristics; Child; Clinical; Coenzyme A; Cognition; Cohort Studies; Complement 3d; Condition; Confidence Intervals; Cross-Sectional Studies; Data; Development; Developmental Disabilities; Diagnosis; Diet; Dietary Intervention; Disease; Early treatment; Enrollment; Epidemiology; Ethnic Origin; Evaluation; Event; Exons; Family; Family Study; Family member; Fasting; Frequencies; Future; Gender; Genes; Goals; Health; Inborn Genetic Diseases; Individual; Infant; Infant formula; Isoleucine; Knowledge; Levocarnitine; Literature; Live Birth; Measures; Medical Surveillance; Metabolism; Minnesota; Molecular; Molecular Genetics; Mutation; Natural History; Neonatal Screening; Neurodevelopmental Impairment; Newborn Infant; Observational Study; Outcome; Oxidoreductase; Parents; Policies; Population; Predictive Value; Prevalence; Procedures; Proteins; Public Health; Regression Analysis; Relative (related person); Reporting; Research Design; Research Personnel; Sampling; Screening Result; Screening procedure; Siblings; Spottings; Standards of Weights and Measures; Stress; Technology; Testing; Vaccination; Variant; Wisconsin; Work; acylcarnitine; base; cohort; design; dietary restriction; disability; follow-up; functional outcomes; gene environment interaction; indexing; neurodevelopment; prevent; programs; prospective; tandem mass spectrometry

DESCRIPTION (provided by applicant): The overall goal of this project is to investigate the prevalence, natural history, and biochemical and molecular characteristics of 2-Methylbutyrl-CoA Dehydrogenase Deficiency (SBCADD) in the Hmong- American population of Wisconsin. SBCADD is a rare inborn error of isoleucine metabolism that may cause neurodevelopmental impairments and can now be identified by state-mandated newborn screening programs using tandem mass spectrometry. During the initial 45 months of newborn screening for MBADD in Wisconsin, 23 cases have been detected, all in infants of Hmong descent. Though procedures are in place for routine newborn screening for SBCADD, neither the natural history of this deficiency nor the utility of early l-carnitine treatment and dietary intervention are known. The proposed project has three specific aims: (1) To analyze newborn screening data from 4/2001-3/2009 to: (a) estimate the prevalence of SBCADD in Hmong and other infants in Wisconsin, (b) describe the distribution of C5-acylcarnitine concentrations in newborn blood specimens, and (c) conduct molecular studies to evaluate the existence of a common SBCADD mutation in this population and to evaluate the current newborn screening cut-off value for detecting this disorder; (2) To test the hypothesis that SBCADD is a benign mutation in the Hmong- American population by conducting observational studies of neurodevelopmental and functional outcomes using three designs: (a) a prospective cohort study of cases identified by newborn screening and matched controls, (b) a cross-sectional study of SBCADD and its outcomes in family members of the infants enrolled in the prospective cohort study, and (c) a correlational analysis to test the hypothesis that persistent C5- acycarnitine blood levels are predictive of adverse developmental outcomes; and (3) To conduct exploratory studies to identify factors associated with adverse outcomes of SBCADD, if such outcomes are observed; potential factors to be examined include diet, triggering events such as illnesses, vaccinations, stress and fasting episodes, and molecular variations and potential gene-environment interactions. The public health significance of this work is that the findings will provide critical information needed to evaluate newborn screening thresholds and policies. The findings may also prompt future studies of the efficacy of early treatment and dietary restriction to prevent developmental disabilities in children with SBCADD.

描述（由申请人提供）： 该项目的总体目的是研究威斯康星州伊斯兰州人口中2-甲基丁基-COA脱氢酶缺乏酶（SBCADD）的患病率，自然史以及生化和分子特征。 SBCADD是异亮氨酸代谢的罕见天生误差，可能会导致神经发育障碍，现在可以使用串联质谱法来识别国家规定的新生儿筛查程序。在威斯康星州的MBADD的最初45个月的新生儿筛查中，已经检测到23例病例，均在苗族下降的婴儿中。尽管已经制定了用于SBCADD的常规新生儿筛查的程序，但这种缺乏的自然历史和早期L-肉碱治疗和饮食干预的效用均不众所周知。拟议的项目具有三个具体目的：（1）分析新出生的筛查数据从4/2001-3/2009分析到：（a）估计hmong中SBCADD的普遍性和威斯康星州的其他婴儿的普遍性，（b）描述C5-酰基苯胺浓度的分布，并在新生儿表标本中进行了公共（C）进行SUMELANS和（C）进行SB的公共（C），并（C）进行了（C）进行SB的公共（C）。评估当前的新生儿筛选截止值以检测这种疾病； （2）通过使用三个设计进行神经发育和功能结果的观察性研究，以测试SBCADD是hmong美国人群中的良性突变：（a）对新生儿筛查和匹配的对照组确定的病例的前瞻性队列研究； （c）一种相关分析，以检验持续性C5-狂热血液水平的假设可预测不良发育结果； （3）进行探索性研究以确定与SBCADD不利结果相关的因素，如果观察到这种结果；要检查的潜在因素包括饮食，触发疾病，疫苗接种，压力和禁食事件以及分子变异以及潜在的基因环境相互作用。这项工作的公共健康意义在于，调查结果将提供评估新生儿筛查阈值和政策所需的关键信息。这些发现还可能促使以后对早期治疗和饮食限制的疗效以防止SBCADD儿童发育障碍的疗效。