Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation

摘要: Objective To determine whether the devastating outcome of neonatal-onset glycine encephalopathy (NKH) could be improved by instituting treatment immediately at birth rather than after symptoms are already well established. Methods A newborn with NKH diagnosed prenatally following neonatal death a previous affected sibling was treated from oral sodium benzoate (250mg/kg/day) and NMDA receptor antagonist ketamine (15mg/kg/day) sampling cord blood cerebrospinal fluid (CSF) for determination. Glycine cleavage system (CGS) activity determined in placental tissue. Mutation analysis performed sequencing all GLDC, GCSH AMT exons. Results CSF (99 μmol/L, reference 3.8–8.0) markedly elevated birth. GCS tissue severely reduced (2.6% controls). A novel homozygous GLDC c.482AG(Y161C) missense mutation identified. Neonatal hypotonia apnea did not occur but long-term poor, intractable seizures severe psychomotor retardation. This contrasts favorable early variant mild deficiency (Ann Neuol 2004;56:139–143). Interpretation Prospective this regimen can favorably modify course does prevent poor outcome, suggesting glycine-induced prenatal injury and/or ongoing postnatal damage. Ann Neurol 2006