Chapter 5 - Disorder: Isovaleric aciduria

Abstract

Isovaleric acidemia (IVA, OMIM #243500) is caused by a deficiency of the enzyme isovaleryl-CoA dehydrogenase (IVDH, EC 1.3.99.10). IVDH is a mitochondrial enzyme that catalyzes the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA, a step in the catabolic pathway of the ketogenic branched-chain amino acid leucine. Mutations in IVDH result in reduced or absent enzyme activity and subsequent inability to properly catabolize leucine, resulting in a buildup of isovaleric acid and related compounds in tissues and body fluids.