目的:探讨中国儿童超长链酰基辅酶A脱氢酶缺乏症(VLCADD)的临床分型、基因型与预后的相关性。
方法:选择2019年2月云南省第一人民医院收治的VLCADD中国家系作为研究对象。疾病的发病特点,对其诊治及预后进行回顾性分析。对相关文献进行了系统的检索和综述。
结果:先证者,一个1岁的男孩,有频繁呕吐的临床表现,低血糖,肝功能和心肌酶异常。串联质谱筛选显示C14、C14:1、C16:1、C16:2、C18和C14/C8显著升高。基因检测显示,他携带了ACADVL基因的复合杂合变体,即c.664G>A(p。G222R)和c.1345G>A(p。E449K),分别来自他的父亲和母亲。患儿被诊断为VLCADD型心肌病,2周后死亡。文献综述已经确定了60名中国儿童VLCADD。临床分类主要为心肌病型和肝病型,占73.3%(43/60)。ACADVL基因变体的组合与VLCAD的临床分类相关。具有一个或两个功能丧失(LOF)突变的儿童表现出更严重的临床表现和更高的死亡率。心肌病类型预后最差,死亡率为76.9%(20/26)。C14:1可作为VLCADD诊断指标,但不能用于临床分型和预后评估。c.1349G>A(p。R450H)变异在中国患者中频率最高,占10.8%(13/120)。
结论:VLCADD的临床分类与预后密切相关,LOF突变在有严重临床表现的患者中更为常见。c.1349G>A(p。R450H)可能是中国患者中最常见的变异,早期筛查和诊断可以大大改善患者的预后。
OBJECTIVE: To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).
METHODS: A Chinese pedigree affected with VLCADD admitted at the First People\'s Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.
RESULTS: The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14:1, C16:1, C16:2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c.664G>A (p.G222R) and c.1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature
review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14:1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c.1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120).
CONCLUSIONS: The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c.1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.