极长链酰基辅酶A脱氢酶缺乏症(VLCAD缺乏症),一种罕见的常染色体隐性疾病,以低酮症低血糖为特征,心肌病,肝损伤,和肌病。VLCAD缺陷是由ACADVL基因缺陷引起的,编码VLCAD蛋白。这项研究的目的是确定临床,生物化学,中国大陆VLCAD缺乏症患者的预后和突变谱.共有六个家庭来拜访我们,4名患者(2男2女)因肝功能障碍入院,低血糖,和阳性新生儿筛查结果。另外两名患者(两名女孩)的父母在他们的孩子死亡后访问我们进行遗传咨询。6例患者血清十四烯酰肉碱(C14:1-肉碱)水平均升高,其中四个显示游离肉碱(C0)水平降低,三个人患有二羧酸尿症。检测到8种类型的ACADVL基因突变,其中三个是小说,包括c.563G>A(p。G188D)c.1387G>A(p。G463R)和c.1582_1586del(p。L529Sfs*31)。p.R450H突变占9/52等位基因(在先前20例无关患者的研究中,和4/12在这项研究中)的基因诊断的中国VLCAD缺乏症病例。四名活着的患者(患者1-4)对饮食预防和药物治疗反应良好,肝功能障碍稳定。总之,我们描述了6个无相关VLCAD缺陷家族中ACADVL基因的3个新突变.此外,我们认为p.R450H可能是中国人群中潜在的热点突变。
Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD deficiency), a rare autosomal recessive disorder, is characterized by hypoketotic hypoglycemia, cardiomyopathy, liver damage, and myopathy. VLCAD deficiency is caused by defects of
ACADVL gene, which encodes VLCAD protein. The aim of this study was to determine the clinical, biochemical, prognosis and mutation spectrum of patients with VLCAD deficiency in mainland China. A total of Six families visited us, four patients (2 boys and 2 girls) were admitted in hospital due to liver dysfunction, hypoglycemia, and positive newborn screen result. The parents of the other two patients (2 girls) visited us for genetic consultation after their children\'s death. All the six patients had elevated level of serum tetradecenoylcarnitine (C14:1-carnitine), four of them showed decreased free carnitine (C0) level, and three had dicarboxylic aciduria. Eight types of mutations of the
ACADVL gene were detected, three of them are novel, including c.563G > A (p.G188D) c.1387G > A (p.G463R) and c.1582_1586del (p.L529Sfs*31). The p.R450H mutation accounts for 9/52 alleles (5/40 in previous study of 20 unrelated patients, and 4/12 in this study) of genetically diagnosed Chinese VLCAD deficiency cases. The four alive patients (Patient 1-4) responded well to diet prevention and drug therapy with stable hepatic dysfunction condition. In conclusion, we describe three novel mutations of the
ACADVL gene among six unrelated families with VLCAD deficiency. Moreover, we suggest that the p.R450H may be a potential hotspot mutation in the Chinese population.