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

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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.