Our results may contribute to understand some of the alterations of CNS development affecting GAMT-deficient patients. Guanidinoacetate methyltransferase (GAMT) deficiency is a neurometabolic disorder characterized by tissue accumulation of guanidinoacetate. Affected patients present with epilepsy and mental retardation whose etiopathogeny is unclear. Since reports have shown that guanidinoacetate alters brain energy metabolism and that creatine, which is depleted in patients with GAMT deficiency, can act as a neuroprotector, in the present study we investigated whether creatine could prevent the alterations of respiratory chain complex II, Na+,K± ATPase and creatine kinase caused by intrastriatal administration of guanidinoacetate in adult rats. Animals were pretreated during 7 days with daily intraperitonial administration of creatine. After, these animals were divided into two groups: Group 1 (sham), rats that suffered surgery and received saline; and group 2 (guanidinoacetatetreated) and they were sacrificed 30 min later. Results showed that the administration of creatine was able to reverse the altered activities of complex II, Na+,K ± ATPase and creatine kinase. These findings indicate that the energy metabolism deficit caused by guanidinoacetate can be prevented by creatine that probably acts as an antioxidant. These data may contribute, at least in part, to a better understanding of the mechanisms related to the energy deficit and oxidative stress found in the GAMT deficiency. Supported by CNPq and FAPERGS. Background: Clinical symptoms of CDS are non specific and measurement of GAA and creatine is an important step for the diagnosis of these diseases.