title: Phenotypic heterogeneity in the syndromes of 3-methylglutaconic aciduria.
abstract: Combined 3-methylglutaconic and 3-methylglutaric aciduria, one of the more common urinary organic acid abnormalities, has been observed in at least three clinical syndromes. We studied an additional seven patients with 3-methylglutaconic aciduria, four of whom were best categorized as having the type II syndrome, two as having an "unspecified" syndrome, and one who may have had a primary urea cycle defect. In cultured cells and autopsy tissues derived from patients with the type II and unspecified syndromes, we were unsuccessful in identifying a defect in the leucine degradative pathway distal to 3-methylcrotonyl-coenzyme A carboxylase and in the cholesterol biosynthetic pathway between 3-hydroxy-3-methylglutaryl-coenzyme A reductase and diphosphomevalonate decarboxylase. Further assessment of the cholesterol biosynthetic pathway in several patients with one of the two types of disease also provided no defined abnormality. The primary metabolic defects in the type II and unspecified syndromes remain undefined.
authors.affiliation: Kimberly H. Courtwright and Joseph W. Summers Metabolic Disease Center, Baylor University Medical Center, Dallas, Texas 75246.
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
authors.forename: W G
authors.initials: WG
authors.lastname: Sherwood
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffman
authors.forename: D A
authors.initials: DA
authors.lastname: Stumpf
authors.forename: I
authors.initials: I
authors.lastname: Dianzani
authors.forename: R B
authors.initials: RB
authors.lastname: Schutgens
authors.forename: P G
authors.initials: PG
authors.lastname: Barth
authors.forename: U
authors.initials: U
authors.lastname: Weismann
authors.forename: C
authors.initials: C
authors.lastname: Bachmann
authors.forename: P
authors.initials: P
authors.lastname: Schrynemackers-Pitance
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000652:urine*; D003065:Coenzyme A / Q000378:metabolism; D005977:Glutarates / Q000378:metabolism* / Q000652:urine; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases; D015093:Meglutol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D010641:Phenotype
chemical_list: D005977:Glutarates; C033686:3-methylglutaric acid; C022034:3-methylglutaconic acid; D015093:Meglutol; D006903:Hydroxymethylglutaryl CoA Reductases; D003065:Coenzyme A