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）： 该项目的总体目标是调查威斯康星州美国苗族人群 2-甲基丁酰辅酶 A 脱氢酶缺乏症 (SBCADD) 的患病率、自然史以及生化和分子特征。 SBCADD 是一种罕见的先天性异亮氨酸代谢缺陷，可能会导致神经发育障碍，现在可以通过国家规定的新生儿筛查项目使用串联质谱法进行识别。在威斯康星州新生儿 MBADD 筛查的最初 45 个月中，已发现 23 例病例，全部为苗族血统的婴儿。尽管有针对 SBCADD 的常规新生儿筛查程序，但这种缺陷的自然史以及早期左旋肉碱治疗和饮食干预的效用尚不清楚。拟议项目有三个具体目标：(1) 分析 2001 年 4 月至 2009 年 3 月的新生儿筛查数据，以：(a) 估计威斯康星州苗族和其他婴儿中 SBCADD 的患病率，(b) 描述 C5 的分布-新生儿血液样本中的酰基肉碱浓度，以及（c）进行分子研究，以评估该人群中是否存在常见的 SBCADD 突变，并评估当前检测该突变的新生儿筛查临界值紊乱； (2) 通过使用三种设计对神经发育和功能结果进行观察性研究，检验 SBCADD 是美国苗族人群中的良性突变的假设：(a) 对通过新生儿筛查和匹配对照确定的病例进行前瞻性队列研究，( b) 对参加前瞻性队列研究的婴儿家庭成员进行 SBCADD 及其结果的横断面研究，以及 (c) 一项相关分析，以检验持续的 C5-乙酰肉碱血液水平可预测不良发育的假设结果； (3) 进行探索性研究，以确定与 SBCADD 不良结果相关的因素（如果观察到此类结果）；需要检查的潜在因素包括饮食、疾病、疫苗接种、压力和禁食等触发事件，以及分子变异和潜在的基因-环境相互作用。这项工作的公共卫生意义在于，研究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未来研究早期治疗和饮食限制对预防 SBCADD 儿童发育障碍的有效性。