Gulati Sheffali, Narayan Chinthana L, Mahesan Aakash, Kamila Gautam, Kapoor Seema, Chaturvedi Pradeep K, Scaria Vinod, Velpandian Thirumurthy, Jauhari Prashant, Chakrabarty Biswaroop, Datta Sudip K R, Pandey R M
Centre of Excellence & Advanced Research for Childhood Neurodevelopmental Disorders, Child Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Division of Genetics, Department of Pediatrics, Maulana Azad Medical College, New Delhi, India.
J Autism Dev Disord. 2024 Sep 4. doi: 10.1007/s10803-024-06542-9.
We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.
我们旨在通过将患有自闭症谱系障碍（ASD）的儿童与正常发育儿童（TDC）对照进行比较，研究转甲基化、氧化应激和线粒体功能障碍的生物标志物在其中的潜在作用。我们还试图将它们与自闭症的严重程度、感觉问题、行为共病以及发育商进行关联。招募了119名患有ASD的儿童和52名年龄及性别匹配的正常发育儿童（TDC）作为对照，排除患有慢性病或正在接受任何抗氧化治疗/多种维生素/抗癫痫药物治疗的儿童。计算了生物标志物的中位数水平——血清同型半胱氨酸、半胱氨酸、蛋氨酸、尿尿酸与肌酐比值、动脉乳酸、血清维生素E、维生素B12、叶酸、Nε-羧甲基赖氨酸、Nω-羧甲基精氨酸（CMA）、二酪氨酸以及亚甲基四氢叶酸还原酶（MTHFR）C677T多态性。使用儿童自闭症评定量表-2、儿童行为清单、儿童感觉概况2照顾者问卷、发育概况3对患有ASD的儿童进行进一步特征分析，以研究与各种生物标志物水平的相关性。ASD组血清同型半胱氨酸的中位数水平为9μmol/L（范围为7 - 16μmol/L），显著高于对照组的7μmol/L（范围为4 - 11μmol/L）（p = 0.01）。ASD患者中高同型半胱氨酸血症（>15μmol/L）的患病率为13.4%，而对照组为3.8%，差异有统计学意义（p = 0.04）。与TDC相比，ASD儿童的二酪氨酸水平更高（9.8对2.2每秒计数（cps），p < 0.001）。高同型半胱氨酸血症的患病率与自闭症的严重程度/发育商/行为问题之间未发现显著相关性。其他生物标志物的中位数水平之间未发现显著差异。结果支持转甲基化缺陷和氧化应激在ASD发病机制中可能发挥的作用。有必要进行进一步研究以更好地理解ASD的发病机制。
