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

3-甲基丁基辅酶a羧化酶（MCC）缺乏症是一种常染色体隐性遗传病亮氨酸分解代谢。表型是高度可变的，范围从新生儿发病与严重的神经受累到无症状的成人。MCC缺乏症是最常见的有机酸尿检测串联质谱（TMS）为基础的新生儿筛查方案。本研究的目的是进一步阐明人类MCC的分子和细胞生物学。我们将对MCCA和MCCB进行分子分析，这两个基因编码MCC的两个亚基，进行表达研究，以确定特定突变的功能后果，并将分子缺陷与受影响患者的临床表型相关联。本研究获得的数据将为开发治疗MCC缺乏症患者的实用指南提供基础。

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.