A single mutation in MCCC1 or MCCC2 as a potential cause of positive screening for 3-methylcrotonyl-CoA carboxylase deficiency

Mol Genet Metab. 2012 Apr;105(4):602-6. doi: 10.1016/j.ymgme.2011.12.018. Epub 2011 Dec 31.

Abstract

Isolated 3-Methylcrotonyl-CoA carboxylase deficiency (MCC deficiency) is an organic aciduria presenting with a highly variable phenotype and has been part of newborn screening programs in various countries, in particular in the US. Here we present enzymatic and genetic characterisation of 22 individuals with increased 3-hydroxyisovalerylcarnitine and/or 3-methylcrotonylglycine suggesting MCC deficiency, but only partially reduced 3-methylcrotonyl-CoA carboxylase activity. Among these, 21 carried a single mutant allele in either MCCC1 (n=20) or MCCC2 (n=1). Our results suggest that heterozygosity for such a single deleterious mutation may lead to misdiagnosis of MCC deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Carbon-Carbon Ligases / deficiency
  • Carbon-Carbon Ligases / genetics*
  • Carnitine / analogs & derivatives
  • Carnitine / metabolism
  • Cells, Cultured
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • Glycine / analogs & derivatives
  • Glycine / metabolism
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation / genetics*
  • Neonatal Screening*
  • Real-Time Polymerase Chain Reaction
  • Skin / cytology
  • Skin / enzymology
  • Urea Cycle Disorders, Inborn / diagnosis*
  • Urea Cycle Disorders, Inborn / genetics*

Substances

  • 3-hydroxyisovalerylcarnitine
  • Acyl Coenzyme A
  • beta-methylcrotonylglycine
  • tiglyl-coenzyme A
  • Carbon-Carbon Ligases
  • methylcrotonoyl-CoA carboxylase
  • Carnitine
  • Glycine

Supplementary concepts

  • 3-methylcrotonyl CoA carboxylase 1 deficiency