Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation
Version of Record online: 10 JAN 2006
Copyright © 2005 American Neurological Association
Annals of Neurology
Volume 59, Issue 2, pages 411–415, February 2006
How to Cite
Korman, S. H., Wexler, I. D., Gutman, A., Rolland, M.-O., Kanno, J. and Kure, S. (2006), Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation. Ann Neurol., 59: 411–415. doi: 10.1002/ana.20759
- Issue online: 25 JAN 2006
- Version of Record online: 10 JAN 2006
- Manuscript Accepted: 24 OCT 2005
- Manuscript Revised: 18 OCT 2005
- Manuscript Received: 27 MAY 2005
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.
A newborn with NKH diagnosed prenatally following the neonatal death of a previous affected sibling was treated from birth with oral sodium benzoate (250mg/kg/day) and the NMDA receptor antagonist ketamine (15mg/kg/day) immediately after sampling cord blood and cerebrospinal fluid (CSF) for glycine determination. Glycine cleavage system (CGS) activity was determined in placental tissue. Mutation analysis was performed by sequencing all GLDC, GCSH and AMT exons.
CSF glycine (99 μmol/L, reference 3.8–8.0) was already markedly elevated at birth. GCS activity in placental tissue was severely reduced (2.6% of controls). A novel homozygous GLDC c.482AG(Y161C) missense mutation was identified. Neonatal hypotonia and apnea did not occur but the long-term outcome was poor, with intractable seizures and severe psychomotor retardation. This contrasts with the favorable outcome with early treatment in variant NKH with mild GCS deficiency (Ann Neuol 2004;56:139–143).
Prospective treatment with this regimen can favorably modify the early neonatal course of severe NKH but does not prevent the poor long-term outcome, suggesting glycine-induced prenatal injury and/or ongoing postnatal damage. Ann Neurol 2006