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Inborn error of amino acid synthesis: Human glutamine synthetase deficiency

  • SSIEM SYMPOSIUM 2005
  • Published:
Journal of Inherited Metabolic Disease

Summary

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.

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Authors and Affiliations

  1. Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, 48129, Münster, Germany

    Johannes Häberle, Frank Rutsch & Hans Georg Koch

  2. Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Boris Görg, Freimut Schliess & Dieter Häussinger

  3. Service de Génétique, Centre Hospitalier Universitaire Bretonneau, 2 boulevard Tonnellé, 37044, Tours Cedex 9, France

    Annick Toutain

  4. Hôpital Robert Debré, Service de Biochimie-Hormonologie, 48, Bd Sérurier, 75019, Paris, France

    Jean-François Benoist

  5. Unité de Neuropathologie, Hôpital Armand Trousseau, 26 avenue du Dr Arnold Netter, 75571, Paris cedex 12, France

    Antoinette Gelot

  6. Département de Pédiatrie, Centre Hospitalier Universitaire Clocheville, 49 boulevard Béranger, 37044, Tours cedex 9, France

    Annie-Laure Suc

Authors
  1. Johannes Häberle
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  2. Boris Görg
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  3. Annick Toutain
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  4. Frank Rutsch
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  5. Jean-François Benoist
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  6. Antoinette Gelot
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  7. Annie-Laure Suc
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  8. Hans Georg Koch
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  9. Freimut Schliess
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  10. Dieter Häussinger
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Corresponding author

Correspondence to Johannes Häberle.

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Communicating editor: Jean-Marie Saudubray

Competing interests: None declared

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Häberle, J., Görg, B., Toutain, A. et al. Inborn error of amino acid synthesis: Human glutamine synthetase deficiency. J Inherit Metab Dis 29, 352–358 (2006). https://doi.org/10.1007/s10545-006-0256-5

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  • DOI: https://doi.org/10.1007/s10545-006-0256-5

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