title: Congenital glutamine deficiency with glutamine synthetase mutations.
abstract: Glutamine synthetase plays a major role in ammonia detoxification, interorgan nitrogen flux, acid-base homeostasis, and cell signaling. We report on two unrelated newborns who had congenital human glutamine synthetase deficiency with severe brain malformations resulting in multiorgan failure and neonatal death. Glutamine was largely absent from their serum, urine, and cerebrospinal fluid. Each infant had a homozygous mutation in the glutamine synthetase gene (R324C and R341C). Studies that used immortalized lymphocytes expressing R324C glutamine synthetase (R324C-GS) and COS7 cells expressing R341C-GS suggest that these mutations are associated with reduced glutamine synthetase activity.
authors.affiliation: Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde und Jugendmedizin, Münster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Boris
authors.initials: B
authors.lastname: Görg
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
authors.forename: Eva
authors.initials: E
authors.lastname: Schmidt
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Benoist
authors.forename: Antoinette
authors.initials: A
authors.lastname: Gelot
authors.forename: Annie-Laure
authors.initials: AL
authors.lastname: Suc
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Höhne
authors.forename: Freimut
authors.initials: F
authors.lastname: Schliess
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Hans G
authors.initials: HG
authors.lastname: Koch
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005973:Glutamine / Q000172:deficiency*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017354:Point Mutation
chemical_list: D005973:Glutamine; D005974:Glutamate-Ammonia Ligase