ABSTRACT
Isovaleric acidemia was first described in 1966 by Tanaka and colleagues [1,2]. It was the unusual odor that led to the recognition of the disorder as an inborn error of metabolism [1,2]. The smell, that of typical volatile, short-chain organic acid, was so recognized by two chemists, L.B. Sjostrim and D. Tokendall, in the original patients. It was then documented as
isovaleric acid by gas chromatography. The molecular defect is in the enzyme, isovaleryl CoA dehydrogenase [3] (Figure 7.1). The gene has been localized to chromosome 15q12-15 [4,5]. Mutations have been reported, including missense point mutations, deletions, and mutations that result in novel processing of this mitochondrial enzyme, such as a variant that causes an mRNA splicing error deleting exon 2 and producing a truncated protein that fails to interact properly with receptors for import into mitochondria [6-9].
