title: Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria.
abstract: 3-Methylglutaconic aciduria is the biochemical marker of several inherited metabolic diseases. Four types of 3-methylglutaconic aciduria can be distinguished. In the type I form, accumulation of 3-methylglutaconate is due to deficient activity of 3-methylglutaconyl-CoA hydratase, an enzyme of the leucine degradation pathway. In the other forms, 3-methylglutaconic acid is not derived from leucine but is of unidentified origin, possibly derived from other metabolic pathways, such as mevalonate metabolism. We report five patients, all presenting a severe early-onset phenotype characterized by 3-methylglutaconic aciduria, hypertrophic cardiomyopathy, cataract, hypotonia/developmental delay, lactic acidosis, and normal 3-methylglutaconyl-CoA hydratase activity. This peculiar phenotype, for which a primary mitochondrial disorder is hypothesized, identifies a novel subtype of 3-methylglutaconic aciduria.
authors.affiliation: Division of Metabolism, Bambino Gesù Children's Research Hospital, Piazza S. Onofrio 4, I-00165, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Rosa
authors.forename: Federica
authors.initials: F
authors.lastname: Deodato
authors.forename: Ference J
authors.initials: FJ
authors.lastname: Loupatty
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rizzo
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Sara
authors.initials: S
authors.lastname: Boenzi
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Andrea
authors.initials: A
authors.lastname: Maiorana
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
mesh_terms: D000140:Acidosis, Lactic / Q000175:diagnosis*; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis*; D001921:Brain / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis*; D002386:Cataract / Q000175:diagnosis*; D002658:Developmental Disabilities / Q000175:diagnosis*; D005192:Family Health; D005260:Female; D005977:Glutarates / Q000652:urine*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree
chemical_list: D005977:Glutarates; C022034:3-methylglutaconic acid