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.
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From the Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde und Jugendmedizin, Münster, Germany (J.H., F.R., E.S., H.G.K.); Heinrich-Heine-University Düsseldorf, Clinic for Gastroenterology, Hepatology and Infectiology, Düsseldorf, Germany (B.G., F.S., D.H.); the Service de Génétique, Centre Hospitalier Universitaire Bretonneau (A.T.), and the Département de Pédiatrie, Centre Hospitalier Universitaire Clocheville (A.-L.S.) — both in Tours, France; the Hôpital Robert Debré, Service de Biochimie-Hormonologie (J.-F.B.), and the Unité de Neuropathologie, Hôpital Armand Trousseau (A.G.) — both in Paris; and the Charité-Universitätsmedizin Berlin, Institut für Biochemie, Berlin (W.H.).
Related Letters:
Congenital Glutamine Deficiency with Glutamine Synthetase Mutations
Kölker S., Hoffmann G. F., Okun J. G., Rose C., Jalan R., Häberle J., Schliess F., Häussinger D.
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N Engl J Med 2006;
354:1093-1094, Mar 9, 2006.
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