The MCCC1 gene is located on 3q27.1 chromosome. It gives instructions for making the alpha subunit of a mitochondrial enzyme called the 3-methylcrotonoyl-CoA carboxylase or 3-MCC. This enzyme consists of 725 amino acids and weighs approximately 81 kDa. The enzyme has six pairs of alpha subunits with smaller beta subunits. The alpha subunit includes the B vitamin biotin binding region, which is required for the enzyme's function.
The 3-MMC enzyme has an important role in leucine and isovaleric acid catabolism. It catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. Defects in this enzyme result in the build-up of leucine byproducts in the body, resulting in the characteristic features of 3-MCC deficiency. These characteristics can range from mild to life-threatening; that include feeding difficulties, recurrent episodes of vomiting and diarrhea, lethargy, and hypotonia.
The MCCC1 gene consists of 19 coding exons, and spans about 101 kb in length. More than 30 different mutations have been identified in patients with 3-methylcrotonyl-CoA carboxylase deficiency. Most of these mutations result in single amino acid changes, which severely reduce or eliminate the activity of the 3-MCC enzyme.
Al-Shamsi et al. (2014) undertook a study to calculate the birth prevalence of IEMs among Emiratis in the UAE by taking into consideration all neonates born with an inherited metabolic condition at Tawam Hospital between 1995 and 2012. Three different mutations were identified in the MCCC1 gene among patients affected with 3-Methylcrotonyl Glycinuria. These included two novel mutations, c.89+2_89+34del and c.1106C>G (p.P369R), and the previously described mutation c.694C>T (p.R232W).