title: Nonketotic hyperglycinemia: treatment with NMDA antagonist and consideration of neuropathogenesis.
abstract: Patients with neonatal-onset nonketotic hyperglycinemia have high-glycine content in cerebrospinal fluid (CSF) which is believed to be a cause of intractable neurologic manifestations. The glycine receptor was believed to be inhibitory in the central nervous system; however, a newly discovered glycine receptor is of the excitatory N-methyl-D-aspartate (NMDA) receptor type, which cannot be antagonized by strychnine. The NMDA receptor antagonist, ketamine, was administered to a patient with nonketotic hyperglycinemia; he demonstrated some improvement in hyperirritability, voluntary movement, and electroencephalographic findings. Strychnine therapy had been administered before this trial of NMDA antagonist, but without improvement. The respiratory condition improved with the reduction of the CSF glycine level after withdrawal of sodium valproate. Our findings indicate that high-glycine content in CSF may affect the brain in different ways via NMDA and classic glycine receptors.
authors.affiliation: Department of Pediatrics, Nagoya University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohya
authors.forename: N
authors.initials: N
authors.lastname: Ochi
authors.forename: N
authors.initials: N
authors.lastname: Mizutani
authors.forename: C
authors.initials: C
authors.lastname: Hayakawa
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D005500:Follow-Up Studies; D005998:Glycine / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013036:Spasms, Infantile / Q000188:drug therapy*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D005998:Glycine