The molecular basis and functional characterization of human 3-methylcrotonyl-CoA carboxylase deficiency

3-甲基巴豆酰-辅酶A羧化酶(MCC)缺乏症是一种常染色体隐性亮氨酸分解代谢紊乱。表型差异很大，从新生儿起病伴有严重的神经系统损害到没有症状的成年人不等。在基于串联质谱仪(TMS)的新生儿筛查程序中，MCC缺乏症是最常见的有机性酸尿。本研究的目的是进一步阐明人MCC的分子和细胞生物学。我们将对编码MCC两个亚单位的两个基因MCCA和MCCB进行分子分析和表达研究，以确定特定突变的功能后果，并将分子缺陷与患者的临床表型相关联。这项研究获得的数据将为制定治疗MCC缺乏症患者的实用指南提供依据。

3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive disorder of leucine catabolism. The phenotype is highly variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. MCC deficiency is the most frequent organic aciduria detected in tandem mass spectrometry (TMS) based newborn screening programs. The aim of this study is to further elucidate the molecular and cellular biology of human MCC. We will perform molecular analyses of MCCA and MCCB, the two genes encoding the two subunits of MCC, expression studies to determine the functional consequences of specific mutations and correlate molecular defects with the clinical phenotype of affected patients. Data obtained in this study will provide the basis for the development of practical guidelines for the treatment of patients with MCC deficiency.