一例肉碱棕榈酰转移酶1A缺乏症患儿的临床及CPT1A基因变异研究

Analysis of a child with carnitine palmitoyl transferase 1A deficiency due to variant of CPT1A gene

目的分析一例肉碱棕榈酰转移酶1A(carnitine palmitoyl transferase 1A,CPT1A)缺乏症患儿的临床资料、代谢筛查和基因变异特征,探讨该病的诊断要点和分子遗传学发病机制。方法收集2018年5月就诊于湖南省儿童医院神经内科的一例以癫痫起病的CPT1A缺乏症患儿的临床资料及其血液酰基肉碱结果,采集患儿和父母外周血,提取DNA行基因检测。结果血液酰基肉碱谱提示游离肉碱(carnitine 0,C0)升高,C0/(C16+C18)明显升高。基因测序结果显示患儿CPT1A基因c.1846G>A和c.2201T>C复合杂合变异,母亲携带c.1846G>A变异,父亲携带c.2201T>C变异。结论本例CPT1A缺乏症患者以癫痫为第一临床表现发病,国内外暂未见相关报道。血液酰基肉碱分析是筛查和诊断CPT1A缺乏症的必要条件,二代测序有助于该病的确诊。CPT1A基因c.1846G>A和c.2201T>C变异可能为该患儿致病原因,c.1846G>A变异为未报道过的新变异,丰富了CPT1A基因变异谱。

Objective To report on the clinical,metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A(CPT1A)deficiency.Methods Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed.Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing(NGS).Results Mass spectrometry of blood acylcarnitine indicated increased carnitine 0(C0)and significantly increased C0/(C16+C18).DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene,namely c.1846G>A and c.2201T>C,which were respectively inherited from her mother and father.Conclusion CPT1A presenting initially as epilepsy was unreported previously.Analysis of blood acylcarnitine C0 and C0/(C16+C18)ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency.The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child.Above finding has also enriched the spectrum of CPT1A gene variants.