3-Methylcrotonyl-CoA carboxylase deficiency: Mutational spectrum derived from comprehensive newborn screening.
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.
Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal. Electronic address: helena.fonseca@insa.min-saude.pt.
Helena
H
Fonseca
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.
Luisa
L
Azevedo
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.
Catarina
C
Serrano
Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
Carmen
C
Sousa
Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
Ana
A
Marcão
Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
Laura
L
Vilarinho
D019735:Carbon-Carbon Ligases / Q000172:deficiency*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D011174:Portugal
D019735:Carbon-Carbon Ligases; C000609234:MCCC1 protein, human; C000609235:methylcrotonoyl-CoA carboxylase 2, human
Biotin-dependent enzyme; Leucine catabolism; MCCC1 and MCCC2 genes; Methylcrotonylglycinuria; Mutational spectrum; National Newborn Screening; Organic aciduria