Congenital glutamine deficiency with glutamine synthetase mutations

N Engl J Med. 2005 Nov 3;353(18):1926-33. doi: 10.1056/NEJMoa050456.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Amino Acid Metabolism, Inborn Errors / pathology
  • Brain / pathology
  • Brain Diseases, Metabolic, Inborn / genetics*
  • Brain Diseases, Metabolic, Inborn / metabolism
  • Brain Diseases, Metabolic, Inborn / pathology
  • DNA Mutational Analysis
  • Fatal Outcome
  • Female
  • Glutamate-Ammonia Ligase / deficiency
  • Glutamate-Ammonia Ligase / genetics*
  • Glutamate-Ammonia Ligase / metabolism
  • Glutamine / deficiency*
  • Humans
  • Infant, Newborn
  • Male
  • Point Mutation*


  • Glutamine
  • Glutamate-Ammonia Ligase