Evaluating Plasma and Urine Porphyrins as Biomarkers of ASD

描述（由申请人提供）：拟议的研究将评估五种卟啉（人类细胞线粒体内产生的化学物质）的血浆和尿液浓度，作为自闭症谱系障碍（ASD）的早期生物标志物。线粒体功能障碍与ASD有关。此外，ASD的早期诊断和干预可以改善儿童的认知表现，语言技能和适应行为。这是公共卫生的目标 该项目表示，拟议的生物标志物将有助于识别儿童作为ASD评估的候选人，从而早期干预并可能改善这些儿童的生活质量。这项拟议中的研究将使用来自加州大学戴维斯分校儿童环境健康中心的遗传学和环境（CHARGE）儿童自闭症风险研究的受试者。受试者年龄均在24 - 60个月之间，入组CHARGE研究，将包括总计828名儿童，其中356名ASD儿童，323名认知和/或适应功能（DD）非ASD发育迟缓儿童作为阳性对照，149名正常发育（TD）儿童作为正常对照。从CHARGE研究保存的冷冻标本中获得血浆和/或尿液等分试样，并使用高压液相色谱法和串联质谱法（HPLC-MS/MS）检测五种卟啉。该项目的目的是证明，使用逻辑回归和受试者工作特征（ROC）分析的组合，这些卟啉可用于识别高达20-33%的ASD病例，与TD对照相比，特异性为98%。将对ASD病例的子集（符合和不符合发育迟缓标准的病例）以及没有ASD的DD儿童进行类似的分析。我们将在我们的分析中包括SES，种族和其他协变量的测量，并评估年龄和性别如何影响敏感性和特异性。由于数据和样品已经收集，我们建议的研究效率会很高。

DESCRIPTION (provided by applicant): The proposed study will evaluate the plasma and urinary concentrations of five porphyrins, chemicals produced within the mitochondria of human cells, as early biomarkers of autism spectrum disorder (ASD). Mitochondrial dysfunction has been implicated in ASD. Furthermore, early diagnosis and intervention in ASD can improve the child's cognitive performance, language skills, and adaptive behavior. It is the public health goal of this project that the proposed biomarker will help identify children as candidates for ASD assessment, leading to earlier intervention and potentially improved quality of life for these children. The proposed study will use subjects from the Childhood Autism Risks from Genetics and Environment (CHARGE) study based at the University of California at Davis' Center for Children's Environmental Health. Subjects, all between 24 and 60 months of age and enrolled in the CHARGE study, will include a total of 828 children, 356 with ASD, 323 with non-ASD developmental delays in cognitive and/or adaptive function (DD) used as positive controls, and 149 typically developing (TD) children used as normal controls. Aliquots of plasma and/or urine will be obtained when available from frozen specimens maintained by the CHARGE study, and will be tested for the five porphyrins using high pressure liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). The aims of this project are to demonstrate, using a combination of logistic regression and receiver operating characteristic (ROC) analysis, that these porphyrins can be used to identify up to 20-33% of ASD cases with a specificity of 98% compared to TD controls. Similar analyses will be conducted on subsets of ASD cases (those who do and do not meet the criteria for developmental delay), as well as the DD children without ASD. We will include measures of SES, ethnicity and other covariates in our analyses, and evaluate how age and gender influence sensitivity and specificity. As the data and specimens have already been collected, the efficiency of our proposed study would be very high.