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名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(1/70 776)。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。
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 283 104 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 SCADD were diagnosed with an incidence of 0.001 4%(1/70 776). There was no obvious abnormality in clinical manifestations. The results showed blood butyl carnitine (C4) level and the ratio of C4 to acetylcarnitine (C2) and propionyl carnitine (C3) raised. 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 0~6.20 mg/g creatinine)], two patients were accompanied by increased lactic acid and one case with increased pyruvic acid. A total of 7 mutations were detected in the ACADS gene. Four were known mutations, three were not reported mutations, all of them were 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 concentration of ethyl malonate acid and C4. Dietary guidance was provided to the SCADD patients. No clinical symptom was found. Normal physical and intellectual development was recorded during the follow-up period. Conclusions The diagnosis of SCADD can be confirmed by the screening of neonatal blood mass spectrometry and gene sequencing. Neonates with early diagnosis and without clinical symptoms have good prognosis.
作者
孙英梅
于春冬
王彩娟
王洪芹
李文杰
SUN Ying-mei;YU Chun-dong;WANG Cai-juan;WANG Hong-qin;LI Wen-jie(Neonatal Screening Laboratory, Qingdao Women and Children s Hospital, Qingdao 266034, China)
出处
《基础医学与临床》
CSCD
2019年第11期1574-1577,共4页
Basic and Clinical Medicine
基金
青岛市医药科研指导计划(2016-WJZD085)
关键词
短链酰基辅酶A脱氢酶缺乏症
串联质谱
基因突变
short chain acyl-CoA dehydrogenase deficiency
tandem mass spectrometry
gene mutation
