Isovaleric acidemia (IVA) is an inborn error of leucine metabolism. The acute neonatal phenotype usually presents within the first 2 weeks of life with poor feeding, vomiting, decreased levels of consciousness, seizures, acidosis and hyperammonemia. A characteristic smell of “sweaty socks” may also be present during an acute illness. A chronic intermittent presentation may occur that is characterized by recurrent episodes of ketoacidosis, vomiting, lethargy, coma and varying degrees of developmental delay. Patients who survive the acute neonatal presentation have a similar clinical course as those with the chronic phenotype. Since the inception of MS/MS based newborn screening, a group of potentially asymptomatic patients has emerged with a mild biochemical phenotype.