A prospective study of mercury toxicity biomarkers in autistic spectrum disorders
A prospective study of mercury toxicity biomarkers in autistic spectrum disorders
复制标题
DOI：
10.1080/15287390701457712
复制
发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Geier, Mark R.
中科院分区：
文献类型：
--
作者：
Geier, David A.;Geier, Mark R.
卟啉是血红素合成途径中形成的衍生物，卟啉提供了一种测量外源性暴露的方法。血红素途径中最容易受到重金属抑制的步骤是尿卟啉脱羧酶（UROD）和粪卟啉原氧化酶（CPOX）反应。汞中毒与尿粪卟啉（cP）、五羧基卟啉（5cxP）和前粪卟啉（prcP）（也称为酮-异粪卟啉）水平升高有关。美国和法国的两组自闭症患者的尿卟啉水平与汞毒性有关。在LabCorp（美国）和Philippe Auguste医院（法国）进行了一项前瞻性尿卟啉检测研究，涉及71名自闭症谱系障碍（ASD）患者、神经典型同胞对照和一般人群对照。ASD患者的尿cP、5cxP和prcP水平相对于对照组显著升高，并且> 50%的ASD患者的尿cP水平高于神经典型同胞对照组的平均值2个标准差以上。在ASD患者中观察到螯合后尿5cxP和cP水平显著降低。在LabCorp和Philippe Auguste医院对ASD患者的尿卟啉测定结果之间存在显著相关性。已确定的汞的发育神经毒性和ASD中汞易感性/毒性的生物化学/基因组证据表明汞的因果作用。尿卟啉检测是临床上可用的，相对便宜，无创。卟啉需要在ASD中进行常规测量，以确定汞毒性是否是致病因素，并评估螯合治疗的有效性。
Porphyrins are derivatives formed in the heme synthesis pathway and porphyrins afford a measure of xenobiotic exposure. The steps in the heme pathway most vulnerable to heavy metal inhibition are uroporphyrin decarboxylase (UROD) and coproporphyrinogen oxidase (CPOX) reactions. Mercury toxicity was associated with elevations in urinary coproporphyrin (cP), pentacarboxyporphyrin (5cxP), and precoproporphyrin (prcP) (also known as keto-isocoproporphyrin) levels. Two cohorts of autistic patients in the United States and France had urine porphyrin levels associated with mercury toxicity. A prospective study of urinary porphyrin testing at LabCorp (United States) and the Laboratoire Philippe Auguste (France) involving 71 autism spectrum disorder (ASD) patients, neurotypical sibling controls, and general population controls was undertaken. ASD patients had significant elevations in urinary levels of cP, 5cxP, and prcP relative to controls, and > 50% of ASD patients had urinary cP levels more than 2 standard deviations above the mean values for neurotypical sibling controls. Significant reductions in urinary 5cxP and cP levels were observed in ASD patients following chelation. A significant correlation was found between urinary porphyrins measured at LabCorp and those measured at the Laboratoire Philippe Auguste on individual ASD patients. The established developmental neurotoxicity attributed to mercury and biochemical/genomic evidence for mercury susceptibility/toxicity in ASDs indicates a causal role for mercury. Urinary porphyrin testing is clinically available, relatively inexpensive, and noninvasive. Porphyrins need to be routinely measured in ASDs to establish if mercury toxicity is a causative factor and to evaluate the effectiveness of chelation therapy.