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目的:对2例生后串联质谱遗传代谢病检测发现疑似中链酰基辅酶A脱氢酶缺乏症的患儿进行临床和基因检测,并进行随访,以明确诊断。方法:采集患儿外周血检测遗传代谢病代谢产物、肝功、采集尿检测尿有机酸,采集患儿及其父母的外周血进行高通量测序和Sanger测序验证中链酰基辅酶A脱氢酶基因ACADM,并对基因异常进行分析。结果:(1)外周血串联质谱LC-MS检测发现患儿中链脂酰肉碱(C6~C10)升高;(2)肝功能均出现异常;(3)尿有机酸检测其中一例患者甘油和双羧酸略有升高,另一例未见异常;(4)基因检测显示患儿均为ACADM基因复合杂合子,基因异常分别来至无症状的单突变携带者父亲和母亲,复合杂合突变导致合成的中链酰基辅酶A脱氢酶活性异常。结论:ACADM基因复合突变导致合成中链酰基辅酶A脱氢酶活性降低,患儿分解中链脂肪酸能力下降,导致代谢产物异常和肝功能异常。
OBJECTIVE: To investigate the clinical and genetic features of 2 cases of suspected mid-chain acyl-CoA dehydrogenase deficiency in the post-natal tandem mass spectrometry genetic and metabolic disease tests and follow-up to confirm the diagnosis. Methods: Peripheral blood of children were collected to detect metabolites of metabolic disease, liver function, urinalysis of urinary organic acids, peripheral blood from children and their parents were collected for high-throughput sequencing and Sanger sequencing to verify the effect of medium chain acyl-CoA dehydrogenase Gene ACADM, and analysis of genetic abnormalities. Results: (1) LC-MS detection of mid-carotenoid (C6-C10) in children with elevated serum levels; (2) Abnormal liver function; (3) And dicarboxylic acid slightly increased, the other cases no abnormalities; (4) gene test showed that all children were ACADM gene heterozygous heterozygous, respectively, to asymptomatic single mutation carriers father and mother, complex heterozygous Mutations result in abnormalities of the synthesized mid-chain acyl-CoA dehydrogenase activity. CONCLUSIONS: Mutation of ACADM gene leads to the decrease of acyl-CoA dehydrogenase activity, and the ability of children to decompose medium chain fatty acids (ACFAs), leading to abnormal metabolites and abnormal liver function.