title: Dextromethorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in an infant.
abstract: To test the hypothesis that nonketotic hyperglycinemia causes overstimulation of the excitatory N-methyl-D-aspartate receptor by allosteric glycine activation, and that reduction of glycine and blocking of the cation channel coupled to the receptor would be beneficial, we administered benzoate and dextromethorphan, a blocker of the N-methyl-D-aspartate channel to an infant with nonketotic hyperglycinemia. Therapy with benzoate, 500 mg/kg per day, was started on day 5, and the dosage was increased to 750 mg/kg per day on day 8, with prompt normalization of the neurologic and electroencephalographic findings. The glycine concentrations in both plasma and cerebrospinal fluid were substantially reduced. Dextromethorphan was added to the regimen on day 12. The electroencephalogram remained normal until the infant was 8 months of age, when diffuse slowing became apparent. Serial brain magnetic resonance imaging showed delayed myelination. At 12 months of age, physical examination findings and growth were normal except for hypotonia. The developmental quotient was approximately 60, and the child was free of seizures. This outcome, although not ideal, is better than that typical for nonketotic hyperglycinemia. Our results suggest that trials with additional patients and other N-methyl-D-aspartate cation channel blockers are warranted.
authors.affiliation: Department of Pediatrics, Howard Hughes Medical Institutes, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: A
authors.initials: A
authors.lastname: Hamosh
authors.forename: J W
authors.initials: JW
authors.lastname: McDonald
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
authors.forename: E
authors.initials: E
authors.lastname: Niedermeyer
authors.forename: M V
authors.initials: MV
authors.lastname: Johnston
mesh_terms: D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D019817:Benzoic Acid; D003915:Dextromethorphan / Q000008:administration & dosage / Q000627:therapeutic use*; D004569:Electroencephalography / Q000187:drug effects; D005998:Glycine / Q000097:blood* / Q000134:cerebrospinal fluid; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007662:Ketosis; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy; D009460:Neurologic Examination; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
chemical_list: D001565:Benzoates; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D019817:Benzoic Acid; D005998:Glycine