3-Methylcrotonyl-CoA carboxylase deficiency: Mutational spectrum derived from comprehensive newborn screening

Gene. 2016 Dec 15;594(2):203-210. doi: 10.1016/j.gene.2016.09.003. Epub 2016 Sep 4.

Abstract

The deficiency of 3-methycrotonyl-CoA carboxylase (3-MCC; EC 6.4.1.4) is an autosomal recessive organic aciduria that is included in the newborn screening programs of several countries. This study reports data mainly obtained from the Portuguese newborn screening program collected over a ten-year period. Analysis of the MCCC1 and MCCC2 genes yielded 26 previously unreported mutations and a variant of clinically unknown significance. These mutations are discussed in the context of their likely impact on the function of the 3-MCC enzyme, with a view to exploring whether a phenotype-genotype correlation might be discerned. Further, these mutations were analysed in the context of what is known of the MCCC1 and MCCC2 mutational spectra, information that will be useful in both clinical and laboratory practice.

Keywords: Biotin-dependent enzyme; Leucine catabolism; MCCC1 and MCCC2 genes; Methylcrotonylglycinuria; Mutational spectrum; National Newborn Screening; Organic aciduria.

MeSH terms

  • Carbon-Carbon Ligases / deficiency*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mass Screening
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics*
  • Mutation*
  • Portugal

Substances

  • Carbon-Carbon Ligases
  • methylcrotonoyl-CoA carboxylase 1, human
  • methylcrotonoyl-CoA carboxylase 2, human