孤独症谱系障碍儿童血清生物学因子水平分析

Analysis of serum biological factors in children with autism spectrum disorder

目的分析孤独症谱系障碍(autism spectrum disorder,ASD)儿童血清铜蓝蛋白(ceruloplasmin,Cp)、同型半胱氨酸(homocysteine,Hcy)、叶酸、血氨(blood ammonia,BA)、铁蛋白(serum ferritin,SF)、乳酸(lactic acid、LA)、微量元素(Fe、Mg、Ca、Zn、Cu、Pd、Cd)及维生素(VA、VE、VD)水平,为ASD儿童的预防和诊治提供理论依据。方法选取2020年1月至2021年5月郑州大学第三附属医院确诊为ASD的184例儿童为ASD组,在儿童发育行为科就诊并最终排除神经发育障碍性疾病的96例儿童为对照组。采用电化学发光免疫分析法测定叶酸、VB12、SF和VD水平,终点法测定BA水平,色谱分析法测定VA、VE水平,酶循环法测定Hcy水平,免疫比浊法测定Cp水平,酶法测定LA水平,原子吸收法测定微量元素水平。结果ASD组儿童的血清Fe[(6.78±0.89)mmol/L比(8.04±0.86)mmol/L]、Mg[(1.56±0.20)mmol/L比(1.61±0.18)mmol/L]、Cu[(15.32±2.68)μmol/L比(18.91±2.77)μmol/L]、叶酸[(26.49±8.15)nmol/L比(33.35±5.40)nmol/L]、VA[0.33(0.29,0.38)mg/L比0.38(0.33,0.41)mg/L]、VD[(43.79±10.85)mg/L比(55.16±3.67)mg/L]和Cp[(304.85±37.11)mg/L比(337.31±37.71)mg/L]水平低于对照组。Ca[(1.79±0.16)mmol/L比(1.56±0.18)mmol/L]、VB12[(722.42±63.53)pmol/L比(700.02±77.45)pmol/L]、BA[(28.40±10.68)μmol/L比(22.98±3.39)μmol/L]、SF[(28.75±11.08)μg/L比(26.18±7.06)μg/L]、Hcy[(7.42±0.46)μmol/L比(6.59±0.61)μmol/L]、VE[(9.27±1.07)mg/L比(8.64±0.99)mg/L]和Pb[27.04(17.40,39.87)μg/L比18.51(7.36,34.20)μg/L]水平高于对照组,差异均有统计学意义(P<0.05)。将单因素筛查有意义的因子纳入二元logistic回归分析显示,Cp(OR=0.988,P=0.037)、Fe(OR=0.124,P=0.000)为ASD的保护性因素,VE(OR=1.704,P=0.008)、BA(OR=1.091,P=0.002)、Ca(OR=65.034,P=0.001)为ASD的独立危险因素。结论与正常儿童相比,ASD儿童Fe、Mg、Cu、叶酸、VA、VD和Cp水平更低,Ca、VB12、BA、SF、Hcy、VE和Pb水平更高;导致ASD发生的因素并不单一,可能有多种因素参与ASD的发病过程。因此寻找ASD的病因,建立有效的预警机制是治疗ASD的根本。

Objective To explore ceruloplasmin(Cp),homocysteine(Hcy),folic acid,blood ammonia(BA),serum ferritin(SF),lactic acid(LA),trace elements and vitamin levels in children with autism spectrum disorder(ASD),providing theoretical basis for the prevention,diagnosis and treatment of children with ASD.Methods A total of 184 children diagnosed with ASD in the Third Affiliated Hospital of Zhengzhou University from January 2020 to May 2021 were enrolled as the ASD group,96 normal children who came to the Department of Pediatric Development and Behavior in the hospital and were eventually excluded from mental developmental disorders were enrolled in the control group.Folic acid,VB12,SF and VD levels were determined by electrochemiluminescence immunoassay.The level of BA was determined by endpoint method.VA and VE levels were determined by chromatography.Hcy was determined by enzyme cycle method.Cp was determined by immunoturbidimetry.Lactic acid was determined by enzymatic method.Determination of trace elements by atomic absorption method.Results The levels of Fe[(6.78±0.89)mmol/L vs.(8.04±0.86)mmol/L],Mg[(1.56±0.20)mmol/L vs.(1.61±0.18)mmol/L],Cu[(15.32±2.68)μmol/L vs.(18.91±2.77)μmol/L],folic acid[(26.49±8.15)nmol/L vs.(33.35±5.40)nmol/L],VD[(43.79±10.85)mg/L vs.(55.16±3.67)mg/L],Cp[(304.85±37.11)mg/L vs.(337.31±37.71)mg/L]and VA[0.33(0.29,0.38)mg/L vs.0.38(0.33,0.41)mg/L]in ASD group were lower than those in the control group,and the differences were statistically significant(P<0.05).The levels of Ca[(1.79±0.16)mmol/L vs.(1.56±0.18)mmol/L],VB12[(722.42±63.53)pmol/L vs.(700.02±77.45)pmol/L],BA[(28.40±10.68)μmol/L vs.(22.98±3.39)μmol/L],SF[(28.75±11.08)μg/L vs.(26.18±7.06)μg/L],Hcy[(7.42±0.46)μmol/L vs.(6.59±0.61)μmol/L],VE[(9.27±1.07)mg/L vs.(8.64±0.99)mg/L]and Pb[27.04(17.40,39.87)μg/L vs.18.51(7.36,34.20)μg/L]were higher than those of the control group,and the differences were statistically significant(P<0.05).The results of binomial logistic regression analysis showed that Cp(OR=0.988,P=0.037)and Fe(OR=0.124,P=0.000)were protective factors for ASD.VE(OR=1.704,P=0.008),BA(OR=1.091,P=0.002),Ca(OR=65.034,P=0.001)were independent risk factors for ASD.Conclusions Compared with normal children,the levels of Fe,Mg,Cu,folic acid,VA,VD and Cp in ASD children are lower.The levels of Ca,VB12,BA,SF,Hcy,VE and Pb are higher,and there may be multiple factors involved in the pathogenesis of ASD.Therefore,finding the cause of ASD and establishing an effective early warning mechanism are fundamental to the treatment of ASD.