Epidemiology of SBCAD Deficiency in Hmong-Americans

该项目的总体目标是调查流行，自然史，生物化学和 苗族2-甲基丁酰辅酶A脱氢酶缺乏症（SBCADD）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缺陷， 神经发育障碍，现在可以通过国家规定的新生儿筛查来识别 程序使用串联质谱。在新生儿MBADD筛查的最初45个月期间， 在威斯康星州，已经发现了23例病例，都是苗族后裔的婴儿。虽然程序在 常规新生儿筛查SBCADD的地方，既没有这种缺陷的自然史，也没有实用性， 早期左旋肉碱治疗和饮食干预是已知的。该项目有三个具体 目的：（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的SBCADD（B）描述了C5-酰基肉毒碱的分布 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 该人群中常见的SBCADD突变，并评估当前新生儿筛查临界值 检测这种疾病;（2）为了检验假设SBCADD是一个良性突变的苗族- 通过对美国人群进行神经发育和功能结局的观察性研究 采用三种设计：（a）对新生儿筛查确定的病例进行前瞻性队列研究， 对照组，（B）SBCADD的横断面研究及其在入选婴儿家庭成员中的结局 在前瞻性队列研究中，以及（c）相关性分析，以检验持续性C5- 无环肉碱血液水平是不良发育结果的预测;和（3）进行探索性研究， 研究以确定与SBCADD不良结局相关的因素（如果观察到此类结局）; 需要检查的潜在因素包括饮食、疾病、疫苗接种、压力和 空腹发作，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，这些发现将为评估新生儿所需的关键信息提供帮助。 筛选阈值和政策。这一发现也可能促进未来对早期化疗疗效的研究。 治疗和饮食限制，以预防SBCADD儿童的发育障碍。

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.