广西中北部地区新生儿脂肪酸氧化障碍酰基肉碱谱筛查及基因检测

Tandem mass spectrometry analysis and genetic diagnosis of neonates with fatty acid oxidation disorders in central and northern regions of Guangxi

目的探讨广西中北部地区新生儿脂肪酸氧化障碍疾病的检出率及疾病分布特点.方法对62953例新生儿进行滤纸干血片酰基肉碱谱筛查,对阳性病例通过尿有机酸分析、Sanger测序或高通量测序进一步进行确诊,明确基因变异的类型.结果共诊断脂肪酸氧化障碍患儿18例,包括原发性肉碱缺乏症13例、肉碱棕榈酰转移酶Ⅱ缺乏症1例、短链酰基辅酶A脱氢酶缺乏症2例、中链酰基辅酶A脱氢酶缺乏症1例、多种酰基辅酶A脱氢酶缺乏症1例.上述病例均通过基因检测确诊,其中ACADS基因c.337G>A(p.Gly113Arg)及ETFA基因c.737G>T(p.Gly246Val)变异位点尚未见文献报道.结论广西中北地区脂肪酸氧化障碍以原发性肉碱缺乏症最为常见.新生儿酰基肉碱谱筛查联合基因检测可在这类疾病的早期进行确诊.

Objective To determine the incidence and mutational types of fatty acid oxidation disorders(FAOD)in central-northern region of Guangxi.Methods A total of 62953 neonates were screened for FAOD during December 2012 and December 2017.Acyl-carnitine profiling of neonatal blood sample was performed by tandem mass spectrometry using dry blood spots on a filter paper.The diagnosis of FAOD was confirmed by organic acid profiling of urea and genetic testing.Results Eighteen cases of FAOD were diagnosed among the 62953 neonates.Among these,primary carnitine deficiency(PCD)was the most common type(n=13),which was followed by shorvchain acyl CoA dehydrogenase deficiency(SCADD)(n=2),medium-chain acyl-CoA dehydrogenase deficiency(MCADD)(n=1),multiple acylCoA dehydrogenase deficiency(MADD)(n 1),and carnitine palmitoyltransferaseⅡdeficiency(CPTⅡD)(n=1).Genetic testing has revealed two previously unreported variants,i.e.,c.337G>A(p.Gly113 Arg)ofACADS gene and c.737G>T(p.Gly246Val)of ETFA gene.Conclusion PCD is the most common FAOD in central northern Guangxi.Tandem mass spectrometry combined with genetic testing may facilitate early diagnosis of FAOD.