Faculty of Psychology and Educational Sciences, Department of Experimental Clinical and Health Psychology, Research in Developmental Disorders Lab, Ghent University, Ghent, Belgium.
Faculty of Medicine and Health Sciences, Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.
PLoS One. 2022 Sep 9;17(9):e0274310. doi: 10.1371/journal.pone.0274310. eCollection 2022.
There is increasing evidence that diseases caused by dysfunctional mitochondria (MD) are associated with autism spectrum disorder (ASD). A comprehensive meta-analysis showed that developmental regression was reported in half of the children with ASD and mitochondrial dysfunction which is much higher than in the general population of ASD. The aim of the present exploratory study was to determine lactate concentrations in urine of children with ASD, as a non-invasive large-scale screening method for metabolic abnormalities including mitochondrial dysfunction and its possible association with regression. First, clinical characteristics of MD were examined in 99 children (3-11 years) with ASD. Second, clinical characteristics of MD, severity of ASD and reported regression were compared between children with the 20% lowest lactate concentrations and those with the 20% highest lactate concentrations in urine. Third, clinical characteristics of MD and lactate concentration in urine were compared in children with (n = 37) and without (n = 62) reported regression. An association of urine lactate concentrations with mitochondrial dysfunction and regression could not be demonstrated in our large ASD cohort. However, since ASD children were reported by their parents to show a broad range of phenotypic characteristics of MD (e.g., gastro-intestinal and respiratory impairments), and lactate concentrations in urine are not always increased in individuals with MD, the presence of milder mitochondrial dysfunction cannot be excluded. Development of alternative biomarkers and their implementation in prospective studies following developmental trajectories of infants at elevated likelihood for ASD will be needed in the future to further unravel the association of ASD with mitochondrial dysfunction and eventually improve early detection.
越来越多的证据表明，功能失调的线粒体（MD）引起的疾病与自闭症谱系障碍（ASD）有关。一项综合荟萃分析显示，一半的 ASD 儿童报告出现发育倒退，而线粒体功能障碍的发病率远高于 ASD 普通人群。本探索性研究的目的是确定 ASD 儿童尿液中的乳酸浓度，作为一种非侵入性的大规模代谢异常筛查方法，包括线粒体功能障碍及其与退行性变化的可能关联。首先，对 99 名（3-11 岁）自闭症儿童的 MD 临床特征进行了检查。其次，将尿液中乳酸浓度最低的 20%儿童和最高的 20%儿童的 MD 临床特征、ASD 严重程度和报告的退行性变化进行了比较。第三，比较了有（n=37）和无（n=62）退行性变化的自闭症儿童的 MD 临床特征和尿液中乳酸浓度。在我们的大型 ASD 队列中，未能证明尿液乳酸浓度与线粒体功能障碍和退行性变化之间存在关联。然而，由于 ASD 儿童被其父母报告表现出广泛的 MD 表型特征（例如，胃肠道和呼吸道损伤），并且并非所有 MD 患者的尿液乳酸浓度都会升高，因此不能排除存在较轻微的线粒体功能障碍。未来需要开发替代生物标志物，并将其应用于前瞻性研究，以追踪具有 ASD 高风险的婴儿的发育轨迹，以进一步阐明 ASD 与线粒体功能障碍的关联，并最终提高早期检测能力。
