Abstract: Objective To explore the relationship between folic acid related metabolites and autism spectrum disorder (ASD), so as to provide theoretical basis for the etiology and pathogenesis of ASD. Methods From June 2017 to December 2018, children who received rehabilitation training in designated rehabilitation institutions for autism in Harbin were collected. Seventy autistic children and seventy matched healthy children were enrolled in this case-control study. The levels of folic acid related metabolites in plasma were measured by liquid chromatography tandem-mass spectrometry (LC-MS/MS), and its association with the clinical phenotype of ASD children was analyzed. Results ASD children had higher plasma levels of cystathionine (Z=2.59), total glutathione (tGSH) (t=5.29), homocysteine (Hcy) (t=2.23), cysteine (t=11.37), methionine (t=3.14) compared to healthy control (P<0.05), but the difference in the levels of adenosine(Z=1.20) and cystine(t=1.75) in plasma between the two groups was not significant (P>0.05). The level of tGSH in ASD children was positively correlated with the scores of social communication score in Social Responsiveness Scale (SRS) (r=0.322, P<0.05). Conclusion Abnormal expression of folic acid related metabolites in ASD children is correlated with the scores of clinical phenotypic features of ASD, and the underlying mechanism needs to be further explored.

Key words: autism spectrum disorder, folic acid related metabolites, case control study

摘要： 目的 探讨叶酸相关代谢物质与孤独症谱系障碍(ASD)的关系,为ASD的病因及发病机制提供线索和理论依据。方法 采用病例对照研究方法,收集2017年6月—2018年12月在哈尔滨市孤独症定点康复机构进行康复训练的ASD儿童70例作为病例组,1∶1性别、年龄匹配的正常儿童作为对照组。应用液相色谱串联质谱(LC-MS/MS)方法检测两组儿童血浆叶酸相关代谢物质水平,并与ASD儿童临床表型特征进行关联分析。结果 ASD组血浆胱硫醚(Z=2.59)、总谷胱甘肽(tGSH)(t=5.29)、同型半胱氨酸(t=2.23)、半胱氨酸(t=11.37)、蛋氨酸(t=3.14)水平均高于对照组(P<0.05),血浆腺苷(Z=1.20)、胱氨酸(t=1.75)水平在两组间的差异无统计学意义(P>0.05)。ASD血浆tGSH与社交反应量表(SRS)中的社交沟通得分呈正相关(r=0.322,P<0.05)。结论 ASD儿童体内叶酸相关代谢物质表达异常,与ASD临床表型特征评分存在相关性,机制有待进一步探讨。

关键词: 孤独症谱系障碍, 叶酸相关代谢物质, 病例对照研究