新发现ACADVL基因突变致极长链酰基辅酶脱氢酶A缺乏症1例患儿的临床特点和基因诊断分析

Genetic analysis of a child with very long chain acyl-CoA dehydrogenase defiviency by a new mutation of ACADVL

目的 对1例极长链酰基辅酶A脱氢酶缺乏症(VLCADD)患儿进行临床特点及基因检测分析。方法 对患儿进行临床评估,以及遗传代谢病串联质谱筛查、家系全外显子组测序(Trios-WES)和Sanger测序验证。结果 患儿出现惊厥伴肝脏体积增大并弥漫性脂肪浸润、心脏彩超左心室壁增厚、代谢性酸中毒、甘油三酯升高等多种临床症状;遗传代谢病串联质谱筛查显示VLCADD相关特征性指标C14∶1持续升高;进一步基因诊断发现患儿存在ACADVL基因复合杂合突变:第5外显子的c.298_299delCA和第7外显子的c.513C>A基因变异,分别来源于父亲及母亲;同时c.513C>A变异为新发现突变。结合患者的临床特征及串联质谱筛查及基因诊断结果,患者符合VLCADD诊断。结论 本研究结果丰富了VLCADD的临床特征和基因突变谱,为临床VLCADD患者的筛查和诊断提供了新的重要依据,为患者父母再生育遗传风险评估和生育干预指导提供了明确依据。

Objective To analyze the clinical characteristics and gene of A child with very long chain acyl-CoA dehydrogenase deficiency(VLCADD).Methods Clinical evaluation,screening by tandem mass spectrometry for genetic metabolic diseases,family whole exome sequencing(TRIOS-WES) and Sanger sequencing were performed.Results Convulsion accompanied by liver enlargement,diffuse fat infiltration,left ventricular wall thickening,metabolic acidosis,triglyceride elevation and other clinical symptoms were observed.Tandem mass spectrometry screening of genetic metabolic disease showed that the characteristic index c14∶1 related to VLCADD increased continuously.Further genetic diagnosis revealed complex heterozygous mutations of ACADVL gene:C.298_299delCA in exon 5 and C.513C>GT in exon 7.A gene variation,respectively from father and mother.At the same time,c.513c>A is a newly discovered mutation.Combined with the clinical characteristics of the patient,tandem mass spectrometry screening and genetic diagnosis results,the patient was consistent with the diagnosis of VLCADD.Conclusion The results of this study enrich the clinical characteristics and gene mutation spectrum of VLCADD,provide a new important basis for the screening and diagnosis of patients with clinical VLCADD,and provide a clear basis for the genetic risk assessment and fertility intervention guidance of patients’ parents.