title: Neurodevelopmental Outcome and Treatment Efficacy of Benzoate and Dextromethorphan in Siblings with Attenuated Nonketotic Hyperglycinemia.
abstract: OBJECTIVE
  To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia.
  
  
  METHODS
  Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures.
  
  
  RESULTS
  In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication.
  
  
  CONCLUSIONS
  Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Kendra J
authors.initials: KJ
authors.lastname: Bjoraker
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Swanson
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Coughlin
authors.affiliation: Western Sydney Genetics Program, Children's Hospital at Westmead, and Disciplines of Pediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.affiliation: Western Sydney Genetics Program, Children's Hospital at Westmead, and Disciplines of Pediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Ee S
authors.initials: ES
authors.lastname: Tan
authors.affiliation: Department of Pediatrics, Oklahoma University, Oklahoma City, OK.
authors.forename: Mark
authors.initials: M
authors.lastname: Fergeson
authors.affiliation: Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dyack
authors.affiliation: Division of Pediatric Genetics, University of Michigan, Ann Arbor, MI.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Marisa W
authors.initials: MW
authors.lastname: Friederich
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Spector
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Geralyn
authors.initials: G
authors.lastname: Creadon-Swindell
authors.affiliation: Child Development Unit, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: M Antoinette
authors.initials: MA
authors.lastname: Hodge
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Sommer
authors.initials: S
authors.lastname: Gaughan
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO.
authors.forename: Casey
authors.initials: C
authors.lastname: Burns
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, CO. Electronic address: Johan.Vanhove@ucdenver.edu.
authors.forename: Johan L K
authors.initials: JL
authors.lastname: Van Hove
mesh_terms: D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003120:Colorado; D057210:Delayed Diagnosis; D003915:Dextromethorphan / Q000627:therapeutic use*; D042241:Early Diagnosis; D004827:Epilepsy / Q000209:etiology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020158:Hyperglycinemia, Nonketotic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D007361:Intelligence Tests; D008297:Male; D009483:Neuropsychological Tests; D035781:Siblings; D020160:Sodium Benzoate / Q000627:therapeutic use*; D061665:Time-to-Treatment
chemical_list: D018691:Excitatory Amino Acid Antagonists; D003915:Dextromethorphan; D020160:Sodium Benzoate