背景:原发性肉碱缺乏症(PCD)是由SLC22A5变异体引起的一种罕见的常染色体隐性脂肪酸氧化障碍,其患病率和SLC22A5基因突变谱因种族和地区而异。本研究旨在系统地分析中国PCD的发病率,并描述PCD和SLC22A5基因变异的患病率的地区差异。
方法:PubMed,Embase,WebofScience,和中国数据库被搜索到2023年11月。在质量评估和数据提取之后,对中国新生儿PCD筛查结果进行了荟萃分析.
结果:在回顾了1,889篇文章之后,包括22项研究,涉及9,958,380例新生儿和476例PCD病例。在476例PCD患者中,469人接受了基因诊断,揭示了SLC22A5的934个等位基因的890个变体,其中检测到107个不同的变体。荟萃分析表明,我国PCD患病率为0.05‰[95CI,(0.04‰,0.06‰)]或1/20000[95CI,(1/16667,1/25000)]。亚组分析显示,中国南方的发病率较高[0.07‰,95CI,(0.05‰,0.08‰)]比中国北方[0.02‰,95CI,(0.02‰,0.03‰)](P<0.001)。此外,荟萃分析的结果表明,变异频率为c.1400C>G,c.51C>G,c.760C>T,c.338G>A,c.428C>T为45%[95CI,(34%,59%)],26%[95CI,(22%,31%)],14%[95CI,(10%,20%)],6%[95CI,(4%,8%)],和5%[95CI,(4%,8%)],分别。在亚组分析中,中国南方c.1400C>G的变异频率[39%,95CI,(29%,53%)]显著低于中国北方[79‰,95CI,(47‰,135‰)](P<0.05)。
结论:本研究系统分析了PCD患病率,并确定了中国人群中常见的SLC22A5基因变异。这些发现为未来新生儿PCD筛查效果提供了有价值的流行病学见解和指导。
BACKGROUND: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants.
METHODS: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns.
RESULTS: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P < 0.05).
CONCLUSIONS: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns.