Epidemiology of SBCAD Deficiency in Hmong-Americans

点击翻译按钮获取中文摘要

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.