title: Creatine metabolism in combined methylmalonic aciduria and homocystinuria.
abstract: Methylation is an important aspect of many fundamental biological processes including creatine biosynthesis. We studied five patients with an inborn error of cobalamin metabolism to characterize the relation between homocysteine and creatine metabolism. Plasma guanidinoacetate concentrations were increased, 14.9 +/- 4.8 micromol/L (p < 0.0001), whereas plasma creatine concentrations were in the low reference range, 43.8 +/- 20.7 micromol/L (p = not significant). Individuals with combined methylmalonic aciduria and homocystinuria have a functional impairment of the creatine synthetic pathway probably secondary to a relative depletion of labile methyl groups. The neurotoxic effects of guanidinoacetate may be partly responsible for the observed neurological phenotype.
authors.affiliation: Unit of Biochemical Genetics, Department of Pediatrics, University of Vienna Children's Hospital, Vienna, Austria. olaf.bodamer@meduniwien.ac.at
authors.forename: Olaf A
authors.initials: OA
authors.lastname: Bodamer
authors.forename: Trilochan
authors.initials: T
authors.lastname: Sahoo
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: William E
authors.initials: WE
authors.lastname: O'Brien
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stöckler-Ipsiroglu
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000032:analysis; D006710:Homocysteine / Q000378:metabolism; D006712:Homocystinuria / Q000378:metabolism*; D006801:Humans; D008297:Male; D008715:Methionine / Q000378:metabolism; D008764:Methylmalonic Acid / Q000097:blood / Q000652:urine*; D014805:Vitamin B 12 / Q000378:metabolism
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D008715:Methionine; C004946:glycocyamine; D003401:Creatine; D014805:Vitamin B 12; D005998:Glycine