title: 3-methylglutaconic acidemia in Smith-Lemli-Opitz syndrome.
abstract: The branched-chain organic acid, 3-methylglutaconic acid, is an intermediate (as the CoA thioester) in the leucine degradative pathway as well as the mevalonate shunt, a pathway that links isoprenoid metabolism with mitochondrial acetyl-CoA metabolism. Because the majority of patients with abnormal 3-methylglutaconic aciduria or acidemia appear to have normal leucine metabolism, we have speculated that some patients with 3-methylglutaconic aciduria may have defects of polyisoprenoid or sterol biosynthesis leading to overflow of isoprenoid precursors to 3-methylglutaconate via the mevalonate shunt. We therefore measured plasma levels of 3-methylglutaconic acid in patients with a known defect of sterol biosynthesis, Smith-Lemli-Opitz syndrome, and found that the patients with the lowest cholesterol levels had abnormally increased plasma levels of 3-methylglutaconic acid, similar in magnitude to those of patients with idiopathic 3-methylglutaconic aciduria. This finding suggests that some patients with unexplained 3-methylglutaconic aciduria may have defects of isoprenoid or sterol biosynthesis underlying their abnormal organic aciduria.
authors.affiliation: Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA.
authors.forename: R I
authors.initials: RI
authors.lastname: Kelley
authors.forename: L
authors.initials: L
authors.lastname: Kratz
mesh_terms: D000293:Adolescent; D002648:Child; D002784:Cholesterol / Q000097:blood; D003684:Dehydrocholesterols / Q000097:blood; D005977:Glutarates / Q000097:blood*; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood*; D013577:Syndrome
chemical_list: D003684:Dehydrocholesterols; D005977:Glutarates; C022034:3-methylglutaconic acid; D002784:Cholesterol; C016705:7-dehydrocholesterol