Biochemical and clinical characteristics of creatine deficiency syndromes.
Creatine deficiency syndromes are a newly described group of inborn errors of creatine synthesis (arginine:glycine amidinotransferase (AGAT) deficiency and guanidinoacetate methyltransferase (GAMT) deficiency) and of creatine transport (creatine transporter (CRTR) deficiency). The common clinical feature of creatine deficiency syndromes is mental retardation and epilepsy suggesting main involvement of cerebral gray matter. The typical biochemical abnormality of creatine deficiency syndromes is cerebral creatine deficiency, which is demonstrated by in vivo proton magnetic resonance spectroscopy. Measurement of guanidinoacetate in body fluids may discriminate between the GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration) deficiencies. Further biochemical characteristics include changes in creatine and creatinine concentrations in body fluids. GAMT and AGAT deficiency are treatable by oral creatine supplementation, while patients with CRTR deficiency do not respond to this type of treatment. The creatine deficiency syndromes are underdiagnosed, so their possibility should be considered in all children affected by unexplained mental retardation, seizures and speech delay.
Sykut-Cegielska
Jolanta
J
Division of Metabolic Diseases, Department of Pedatrics, Children's Memorial Health Institute, Warsaw, Poland.
Gradowska
Wanda
W
Mercimek-Mahmutoglu
Saadet
S
Stöckler-Ipsiroglu
Sylvia
S
D000579:Amidinotransferases / Q000096:biosynthesis; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy; D003401:Creatine / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050937:Guanidinoacetate N-Methyltransferase; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D008780:Methyltransferases / Q000096:biosynthesis
D026901:Membrane Transport Proteins; C080679:creatine transporter; D008780:Methyltransferases; C494506:GAMT protein, human; D050937:Guanidinoacetate N-Methyltransferase; D000579:Amidinotransferases; D003401:Creatine