Conclusions: Gly induces lipid and protein oxidative damage and also modulates the activity of antioxidant enzymes in striatum. In case these findings also occur in human NKH, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this disease. Pérez-Cerdá C 1 , Navarrete R 1 , Sanz P 1 , Garcia Muñoz F 1 , Rodríguez-Pombo P 1 , Ugarte M 1 1 CEDEM,CBM,CIBERER,Univ Autonoma Madrid, MADRID, Spain NKH is caused by deficiency of the glycine cleavage multi-enzyme system (GCS) with three specific components encoded by GLDC, AMT, and GCSH. It is characterized by accumulation of glycine in body fluids and various neurological symptoms. In this study, we analyzed the mutation spectrum of twenty-two NKH patients grouped by clinical and biochemical findings as three subgroups: sixteen patients with neonatal presentation of convulsions and displaying high levels of CSF-glycine (88-246 μM); two cases with infantile outcome (CSF-glycine 24-26 μM); four patients with infantile onset, CSF-glycine from 12-34 μM and progressive neurological disease leading to death. The genetic screening included the exonsequencing analysis of GCS genes and a multiplex ligation-dependent probe amplification to detect GLDC deletions. GLDC mutations were identified in 15 of the 16 neonatal-onset NKH. The spectrum included six different types of GLDC deletions mostly affecting regions comprising exons 1-15 and 17 potential-pathogenic point mutations. Three different mutations in AMT gene were found in two patients; one neonatal (p.