Biochemical and molecular characterization of 3-Methylcrotonylglycinuria in an Italian asymptomatic girl

3-Methylcrotonylglycinuria is an organic aciduria resulting from deficiency of 3-methylcrotonyl-CoA carboxylase (3-MCC), a biotin-dependent mitochondrial enzyme carboxylating 3-methylcrotonil-CoA to 3-methylglutaconyl-CoA during leucine catabolism. Its deficiency, due to mutations on MCCC1 and MCCC2 genes, leads to accumulation in blood and/or urine of 3-hydroxyisovaleryl-carnitine (C5OH) in plasma and 3-methylcrotonyl-glycine and 3-hydroxyisovaleric acid in the urine. The phenotype of 3-MCC deficiency is highly variable, ranging from severe neurological abnormalities and death in infancy to asymptomatic adults. Here we report the biochemical and molecular characterization of an Italian asymptomatic female child, positive to the newborn screening, for which molecular analysis showed two severe mutations in MCCC2 gene, one missense mutation, c.691A>T (p.I231F), and one unknown splicing mutation, c.1150-1G>A. We characterized the expression profile of the novel splice mutation by functional studies.