Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle

• Published in: Molecular genetics and metabolism Vol. 82; no. 3; pp. 208 - 213
• Main Authors: Ensenauer, R, Thiel, T, Schwab, K.O, Tacke, U, Stöckler-Ipsiroglu, S, Schulze, A, Hennig, J, Lehnert, W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2004
• Subjects: Arginine - blood; Arginine restriction; Brain - metabolism; Child; Creatine - cerebrospinal fluid; Creatine - metabolism; Creatine - therapeutic use; Creatine deficiency; Creatinine - blood; Creatinine - urine; Gas Chromatography-Mass Spectrometry; Glycine - analogs & derivatives; Glycine - blood; Glycine - cerebrospinal fluid; Glycine - urine; Guanidinoacetate methyltransferase; Guanidinoacetate N-Methyltransferase; Humans; Intermittent high-dose creatine therapy; Magnetic Resonance Spectroscopy; Male; Methyltransferases - deficiency; Muscle, Skeletal - metabolism; Ornithine - blood; Ornithine supplementation; Phosphocreatine - metabolism; Phosphorus magnetic resonance spectroscopy; Proton magnetic resonance spectroscopy; Skeletal muscle; Turkey; Turkey; Creatine deficiency; Intermittent high-dose creatine therapy; Proton magnetic resonance spectroscopy; Guanidinoacetate methyltransferase; Arginine restriction; Phosphorus magnetic resonance spectroscopy; Ornithine supplementation; Skeletal muscle
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2004.04.005

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.