摘要目的 了解新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)患病率、临床特征及基因突变特点.方法 采用串联质谱技术,对2009年1月到2015年10月1 430 024例新生儿进行遗传代谢病筛查,对筛查出的疑似SCADD患儿通过尿有机酸分析,酰基辅酶A脱氢酶编码基因(ACADS)进行确诊,对确诊病例分析其临床、生化改变及基因突变特点,进行饮食指导、生活管理及补充左旋肉碱,随访观察其生长及智能发育情况.结果 确诊SCADD 17例,患病率为1/84 117.患儿无临床症状,血丁酰基肉碱(C4)及其与乙酰基肉碱(C2),丙酰基肉碱(C3)比值均增高,C40.71 ～3.14 μmol/L(正常值0.03 ～0.48 μmol/L),C4/C20.07～0.23(正常值0.01 ～0.04),C4/C30.65 ～2.04(正常值0.05 ～0.39).尿有机酸分析13例,乙基丙二酸均增高[9.30 ～ 90.99 mg/g肌酐(正常值0～6.20mg/g肌酐)],1例伴甲基琥珀酸增高[12.33 mg/g肌酐(正常值0～6.40 mg/g肌酐)],1例伴乙酰甘氨酸增高[3.52 mg/g肌酐(正常值0～0.70 mg/g肌酐)].发现ACADS基因突变13种,其中12种为错义突变,1种为移码突变,均为已知突变.1例为纯合突变(c.1031A＞ G),其余为复合杂合突变.常见突变为c.1031A ＞G(35.3％)与c.164C＞ T(20.6％),ACADS基因型与乙基丙二酸以及C4浓度水平无明显相关.对患儿随访8 ～42个月,均未出现临床症状,体格及智力发育正常.结论 SCADD在新生儿人群中患病率为1/84 117.通过新生儿筛查确诊的SCADD无临床症状.常见基因突变为c.1031A＞G与c.164C＞T.

abstractsObjective To investigate the incidence,clinical,biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency (SCADD).Method From January,2009 to October,2015,a retrospective analysis of the urine organic acids and acyl-coenzyme A dehydrogenase (ACADS) gene mutation characteristics of patients diagnosed as SCADD by newborn screening using tandem mass spectrometry in Department of Genetics and Metabolism (Newborn screening Center of Zhejiang Province),Children's Hospital,Zhejiang University School of Medicine.Dietary guidance,life management and supplementation of L-carnitine were conducted,and growth and intelligence development were observed during follow-up among the SCADD patients.Result A total of 1 430 024 neonates,seventeen cases were diagnosed with SCADD with an incidence of 1/84 117.All patients had no clinical symptoms,and intelligence and physical development were normal.Blood butylacyl-carnitine (C4) levels and the ratios increased,C4 0.713.14 μmol/L (reference value 0.03-0.48 μmol/L),C4/C2 0.07-0.23(reference value 0.01-0.04),C4/C30.65-2.04(reference value 0.05-0.39).Thirteen with increased urinary ethyl malonic acid (9.30-90.99 mg/g creatinine (reference value 0-6.20 mg/g creatinine)),one patient was accompanied by increased methyl succinic acid (12.33 mg,/g creatinine (reference value 0-6.40 mg/g creatinine)),one subject with increased acetylglycine (3.52 mg/g creatinine (reference value 0-0.70 mg/g creatinine)).A total of 13 known mutations were detected in the ACADS gene,1 homozygous mutation (c.1031A ＞ G),the others are compound heterozygous mutations.One frameshift mutation (c.508_509delGC) and 12 missense mutations were detected.Common mutation were c.1031A ＞ G (35.3％),c.164C ＞ T (20.6％) and c.991G ＞ A (11.8％).SCADD in newborn screening program had no clinical symptoms and normal growth development after 8-42 months follow-up.Conclusion Cases with SCADD had no clinical symptoms with an incidence of 1/84117.The c.164C ＞ T and c.1031A ＞ G may be the common mutations.