title: Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle.
abstract: Deficiency of guanidinoacetate methyltransferase (GAMT), the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate in brain. This results in epilepsy, mental retardation, and extrapyramidal movement disorders. Investigation of skeletal muscle by proton and phosphorus magnetic resonance spectroscopy before therapy demonstrated the presence of considerable amounts of creatine and phosphocreatine, and accumulation of phosphorylated guanidinoacetate in a 7-year-old boy diagnosed with GAMT deficiency, suggesting separate mechanisms for creatine uptake and synthesis in brain and skeletal muscle. The combination of creatine supplementation and a guanidinoacetate-lowering therapeutic approach resulted in improvement of clinical symptoms and metabolite concentrations in brain, muscle, and body fluids.
authors.affiliation: Metabolic Unit, University Children's Hospital, Freiburg, Germany. ensenauer.regina@mayo.edu
authors.forename: R
authors.initials: R
authors.lastname: Ensenauer
authors.forename: T
authors.initials: T
authors.lastname: Thiel
authors.forename: K O
authors.initials: KO
authors.lastname: Schwab
authors.forename: U
authors.initials: U
authors.lastname: Tacke
authors.forename: S
authors.initials: S
authors.lastname: Stöckler-Ipsiroglu
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: J
authors.initials: J
authors.lastname: Hennig
authors.forename: W
authors.initials: W
authors.lastname: Lehnert
mesh_terms: D001120:Arginine / Q000097:blood; D001921:Brain / Q000378:metabolism*; D002648:Child; D003401:Creatine / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D050937:Guanidinoacetate N-Methyltransferase; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008780:Methyltransferases / Q000172:deficiency*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009952:Ornithine / Q000097:blood; D010725:Phosphocreatine / Q000378:metabolism; D014421:Turkey
chemical_list: D010725:Phosphocreatine; D001120:Arginine; D003404:Creatinine; D009952:Ornithine; D008780:Methyltransferases; C494506:GAMT protein, human; D050937:Guanidinoacetate N-Methyltransferase; C004946:glycocyamine; D003401:Creatine; D005998:Glycine