[4] Manifestations of 3-Methylcrotonyl-CoA carboxylase deficiency range from asymptomatic[5] to neonatal onset with extreme neurological symptoms[6] and even fatal cases.

The diagnosis of 3-Methylcrotonyl-CoA carboxylase deficiency is confirmed by decreased enzyme activity in fibroblasts or white blood cells.

[12] 3-Methylcrotonyl-CoA carboxylase deficiency is the most common organic aciduria detected by newborn screening programs in Australia,[13] North America,[14] and Europe.

[15] Those with 3-Methylcrotonyl-CoA carboxylase deficiency typically display normal development until 6 months to 3 years old when patients present with an acute episode.

[5] Manifestations of 3-Methylcrotonyl-CoA carboxylase deficiency vary even among family members who share a common environment and genetics.

If a mutation in the MCCC1 or MCCC2 gene reduces or eliminates the activity of 3-methylcrotonyl-CoA carboxylase, the body is unable to process leucine properly.

As a result, toxic byproducts of leucine processing build up to harmful levels, damaging the brain and nervous system.