3-Methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive inborn error of leucine metabolism, caused by mutations in either MCCC1 or MCCC2 gene. We identified eight novel mutations of MCCC1 or MCCC2 in six Chinese newborns screened by tandem mass spectrometry. Transcript analysis revealed that the novel splice mutation c.639+5G>T produced a normal transcript and a transcript of exon 6 skipping which led to truncated MCCC1 protein. The remaining seven novel mutations may cause structure damage and dysfunction of MCC as predicted by in silico analysis. In conclusion, our study expands the spectrum of mutations found in MCCC1 and MCCC2 and provides a rough prevalence of 1 of 68,333 in Chinese population. Although the affected patients remained asymptomatic during follow-up, we hold the view that early detection through newborn screening, early intervention and follow-up may provide an important guidance to prevent subsequent metabolic disorders and deal with crisis later in life.
Keywords: 3-methylcrotonyl-CoA carboxylase deficiency; Chinese population; mutation; newborn screening.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.