Epidemiology of SBCAD Deficiency in Hmong-Americans

该项目的总体目标是调查患病率、自然病史、生化和 苗族2-甲基丁酰-辅酶A脱氢酶缺乏症的分子特征 威斯康星州的美国人口。SBCADD是一种罕见的先天性异亮氨酸代谢错误，可能导致 神经发育障碍，现在可以通过国家强制新生儿筛查来识别 使用串联质谱学的程序。在新生儿MBADD筛查的最初45个月期间 在威斯康星州，已发现23例病例，均为苗族血统的婴儿。尽管程序已经在 SBCADD常规新生儿筛查的地点，既不是这种缺陷的自然病史，也不是实用价值 L的早期--肉碱治疗和饮食干预是已知的。拟议的项目有三个具体的 目标：(1)分析2001年4月至2009年3月的新生儿筛查数据，以：(A)估计患病率 在苗族和威斯康星州其他婴儿中的SBCADD，(B)描述C5-酰卡尼汀的分布 新生儿血液样本中的浓度，以及(C)进行分子研究，以评估是否存在 该人群中一种常见的SBCADD突变，并评估当前新生儿筛查的临界值 用于检测这种疾病；(2)检验SBCADD是苗族人良性突变的假设- 通过对神经发育和功能结果进行观察性研究来研究美国人口 使用三个设计：(A)对新生儿筛查和匹配的病例进行前瞻性队列研究 对照，(B)对登记婴儿的家庭成员进行SBCADD及其结局的横断面研究 在前瞻性队列研究中，以及(C)相关分析，以检验持续C5- 阿昔卡尼汀水平可预测不良发育结局；以及(3)进行探索性研究 研究确定与SBCADD不良结果相关的因素，如果观察到此类结果的话； 需要检查的潜在因素包括饮食、引发疾病、接种疫苗、压力和 禁食时期，以及分子变异和潜在的基因-环境相互作用。公共卫生 这项工作的意义在于，这些发现将提供评估新生儿所需的关键信息 筛选门槛和政策。这一发现还可能促使未来对早期治疗的有效性进行研究 预防SBCADD儿童发育障碍的治疗和饮食限制。

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.