Primary and maternal 3-methylcrotonyl-CoA carboxylase deficiency: insights from the Israel newborn screening program
Primary and maternal 3-methylcrotonyl-CoA carboxylase deficiency: insights from the Israel newborn screening program
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DOI：
10.1007/s10545-015-9899-4
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发表时间：
2016-03-01
影响因子：
4.2
通讯作者：
Spiegel, Ronen
中科院分区：
文献类型：
--
作者：
Rips, Jonathan;Almashanu, Shlomo;Spiegel, Ronen
背景3-甲基丁基辅酶a羧化酶缺乏症（3MCCD）是一种先天性亮氨酸分解代谢错误。全球新生儿串联质谱筛查（NBS）项目证实3MCCD是最常见的有机酸尿症，是一种相对良性的疾病，预后良好。此外，一些无症状的3MCCD母亲最初是在对其健康婴儿进行异常筛查后被发现的，并被恰当地称为母亲3MCCD。方法：本研究是一项回顾性研究，总结了自2009年以色列扩展NBS项目引入以来，通过问卷调查收集的所有3MCCD个体的临床、生化和遗传数据，包括孕产妇3MCCD病例。结果在50个月的研究期间，共有36例3MCCD患者被确诊；16例为原发性病例，20例为产妇病例。在兄弟姐妹筛查后，又发现了4例3MCCD患者。所有母亲3MCCD病例均无症状，除了一位母亲表现出儿童低张力。大多数原发性3MCCD患者无症状，但有两例伴有严重早产。3MCCD母亲所生的新生儿初始干血斑（DBS）游离肉碱明显低于原发性3MCCD母亲所生的新生儿（p=0.0009）。在MCCC1和MCCC2基因中发现的大多数突变是错义的，其中5个是新突变。结论产妇3MCCD比以前认为的更常见，其存在可能最初表明低DBS游离肉碱水平。我们的研究结果进一步证实了3MCCD的良性本质，我们建议将这种疾病排除在NBS计划之外。
Background 3-Methylcrotonyl-CoA carboxylase deficiency (3MCCD) is an inborn error of leucine catabolism. Tandem mass spectrometry newborn screening (NBS) programs worldwide confirmed 3MCCD to be the most common organic aciduria and a relatively benign disorder with favorable outcome. In addition, several asymptomatic 3MCCD mothers were initially identified following abnormal screening of their healthy babies and were appropriately termed maternal 3MCCD.Methods This is a retrospective study that summarizes all the clinical, biochemical, and genetic data collected by questionnaires of all 3MCCD individuals that were identified by the extended Israeli NBS program since its introduction in 2009 including maternal 3MCCD cases.Results A total of 36 3MCCD subjects were diagnosed within the 50-month study period; 16 were classified primary and 20 maternal cases. Four additional 3MCCD individuals were identified following sibling screening. All maternal 3MCCD cases were asymptomatic except for one mother who manifested childhood hypotonia. Most of the primary 3MCCD individuals were asymptomatic except for two whose condition was also complicated by severe prematurity. Initial dried blood spot (DBS) free carnitine was significantly lower in neonates born to 3MCCD mothers compared with newborns with primary 3MCCD (p=0.0009). Most of the mutations identified in the MCCC1 and MCCC2 genes were missense, five of them were novel.Conclusions Maternal 3MCCD is more common than previously thought and its presence may be initially indicated by low DBS free carnitine levels. Our findings provide additional confirmation of the benign nature of 3MCCD and we suggest to exclude this disorder from NBS programs.