Congenital glutamine deficiency with glutamine synthetase mutations.
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.
Häberle
Johannes
J
Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde und Jugendmedizin, Münster, Germany.
Görg
Boris
B
Rutsch
Frank
F
Schmidt
Eva
E
Toutain
Annick
A
Benoist
Jean-François
JF
Gelot
Antoinette
A
Suc
Annie-Laure
AL
Höhne
Wolfgang
W
Schliess
Freimut
F
Häussinger
Dieter
D
Koch
Hans G
HG
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
D005973:Glutamine; D005974:Glutamate-Ammonia Ligase