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

Helena Fonseca; Luisa Azevedo; Catarina Serrano; Carmen Sousa; Ana Marcão; Laura Vilarinho

doi:10.1016/j.gene.2016.09.003

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.

Authors

Helena Fonseca¹, Luisa Azevedo², Catarina Serrano³, Carmen Sousa⁴, Ana Marcão⁴, Laura Vilarinho⁴

Affiliations

¹ Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal. Electronic address: [email protected].
² Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Population Genetics and Evolution, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.
³ Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Population Genetics and Evolution, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
⁴ Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.

PMID: 27601257
DOI: 10.1016/j.gene.2016.09.003

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