title: Inborn error of amino acid synthesis: human glutamine synthetase deficiency.
abstract: Glutamine synthetase (GS) is ubiquitously expressed in human tissues, being involved in ammonia detoxification and interorgan nitrogen flux. Inherited systemic deficiency of glutamine based on a defect of glutamine synthetase was recently described in two newborns with an early fatal course of disease. Glutamine was largely absent in their serum, urine and cerebrospinal fluid. Each of the patients had a homozygous mutation in the glutamine synthetase gene and enzymatic investigations confirmed that these mutations lead to a severely reduced glutamine synthetase activity. From the observation in the first patients with congenital glutamine synthetase deficiency, brain malformation can be expected as one of the leading signs. In addition, other organ systems are probably involved as observed in one of the index patients who suffered from severe enteropathy and necrolytic erythema of the skin. Deficiency of GS has to be added to the list of inherited metabolic disorders as a rare example of a defect in the biosynthesis of an amino acid.
authors.affiliation: Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, 48129, Münster, Germany. haeb@uni-muenster.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Boris
authors.initials: B
authors.lastname: Görg
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
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: Hans Georg
authors.initials: HG
authors.lastname: Koch
authors.forename: Freimut
authors.initials: F
authors.lastname: Schliess
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000002:abnormalities; D003677:Deficiency Diseases / Q000209:etiology; D017809:Fatal Outcome; D005260:Female; D047109:Fetal Development; D005974:Glutamate-Ammonia Ligase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology; D016031:Liver Transplantation / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology; D009154:Mutation; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000473:pathology
chemical_list: D005973:Glutamine; D005974:Glutamate-Ammonia Ligase