3-methylcrotonyl-CoA carboxylase 1 deficiency

3-Methylcrotonyl-CoA carboxylase deficiency

3-Methylcrotonyl-CoA carboxylase deficiency also known as 3-Methylcrotonylglycinuria is an inborn error of leucine metabolism and is inherited through an autosomal recessive fashion. 3-Methylcrotonyl-CoA carboxylase deficiency is caused by mutations in the MCCC1 gene, formerly known as MMCA, or the MCCC2 gene, formerly known as MCCB. MCCC1 encodes the a-subunits of 3-methylcrotonyl-CoA carboxylase while MCCC2 encodes the b-subunits. The clinical presentation of 3-Methylcrotonyl-CoA carboxylase deficiency is varied, even within members of the same family. Manifestations of 3-Methylcrotonyl-CoA carboxylase deficiency range from asymptomatic to neonatal onset with extreme neurological symptoms and even fatal cases. 3-Methylcrotonyl-CoA carboxylase deficiency is diagnosed by increased 3-hydroxyisovaleric acid and 3-methylcrotonylglycine in the urine. 3-hydroxyisovalerylcarnitine is often found in both the urine and blood. The diagnosis of 3-Methylcrotonyl-CoA carboxylase deficiency is confirmed by decreased enzyme activity in fibroblasts or white blood cells. Although no treatment options have been proven to help manage 3-Methylcrotonyl-CoA carboxylase deficiency proposed treatments include L-carnitine supplements, glycine administration, biotin supplements and dietary restriction of leucine. 3-Methylcrotonyl-CoA carboxylase deficiency is the most common organic aciduria detected by newborn screening programs in Australia, North America, and Europe.