›› 2019, Vol. 39 ›› Issue (11): 1574-1577.

• 研究论文 • 上一篇    下一篇



  1. 青岛市妇女儿童医院
  • 收稿日期:2019-02-20 修回日期:2019-04-26 出版日期:2019-11-05 发布日期:2019-11-05
  • 通讯作者: 李文杰 E-mail:qdgcms@126.com
  • 基金资助:

Analysis of clinical and gene mutation characteristics in four patients with short chain acyl-CoA dehydrogenase deficiency

  • Received:2019-02-20 Revised:2019-04-26 Online:2019-11-05 Published:2019-11-05

摘要: 目的 探讨青岛地区新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)患儿的临床特征及基因突变特点。 方法 利用串联质谱技术检测283 104例新生儿干血滤纸片中酰基肉碱水平,对筛查出的疑似SCADD患儿通过尿有机酸检测、短链酰基辅酶A脱氢酶(ACADS)突变检测进行确诊。 结果 共确诊4例短链酰基辅酶A脱氢酶缺乏症患儿,患病率1.4/10万(1/70776)。患儿临床表现无明显异常,串联质谱检测显示血丁酰基肉碱(C4)及其与乙酰肉碱(C2)、丙酰肉碱(C3)比值均增高。对4例患儿进行尿有机酸分析,乙基丙二酸均增高[8.41~36.34 mg/g肌酐(正常值0~6.20 mg/g肌酐)],还有2例伴乳酸增高,1例伴丙酮酸增高。基因测序共发现7种ACADS突变,4种为已知突变,3种未报道突变,均为错义突变。4例患儿均为复合杂合突变,分别为:c.1031A>G/c.989G>A;c.1186G>A/c.1195C>T;c.1031A>G/c.445A>T;c.1130C>T/ c.1157G>A。常见突变为c.1031A>G(25%),ACADS基因型与乙基丙二酸以及C4浓度水平无明显相关。对患儿进行饮食指导,随访均未出现临床症状,体格及智力发育正常。 结论 通过血串联质谱筛查配合基因测序可以对SCADD明确诊断,早期确诊的新生儿无临床症状,预后较好。

关键词: 短链酰基辅酶A脱氢酶缺乏症, 串联质谱, 基因突变

Abstract: Objective To investigate the clinical and gene mutation characteristics of short chain acyl-CoA dehydrogenase deficiency(SCADD) in Qingdao area. Methods The acylcarnitine levels in the blood of 283104 neonates from newborns screening program were measured by tandem mass spectrometry. The suspected SCADD neonates were diagnosed by retrospective analysis of the urine organic acids and short chain acyl-CoA dehydrogenase (ACADS) gene mutation characteristics. Results Four cases of short chain acyl-CoA dehydrogenase deficiency(SCADD)were diagnosed, with an incidence of 0.0014%(1/70776). There was no obvious abnormality in clinical manifestations. The results showed blood butyl carnitine (C4) levels and the ratios of C4 to acetylcarnitine (C2) and propionyl carnitine (C3) increased. Urinary organic acids were analyzed in 4 cases, all of which ethyl malonate acid was increased [8.41~36.34 mg/g creatinine (reference value 0~6.20mg/g creatinine)], two patients were accompanied by increased lactic acid and one subiect with increased pyruvic acid. A total of 7 mutations were detected in the ACADS gene. Four are known mutations, three are not reported mutations, all of them are missense mutations. The 4 patients were all compound heterozygous mutations: c.1031A>G/c.989G>A;c.1186G>A/c.1195C>T;c.1031A>G/c.445A>T;c.1130C>T/ c.1157G>A。Common mutation was c.1031A>G(25%). The ACADS genotype was not significantly correlated with the concentrations of ethyl malonate acid and C4. Dietary guidance was provided to the SCADD patients. No clinical symptoms and normal physical and intellectual development occurred during the follow-up period. Conclusions The diagnosis of SCADD can be confirmed by the screening of neonatal blood mass spectrometry and gene sequencing. Early diagnosis of neonates without clinical symptoms and the prognosis is good.

Key words: Short chain acyl-CoA dehydrogenase deficiency, Tandem mass spectrometry, Gene mutation