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Genetics Home Reference: your guide to understanding genetic conditions
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Glutathione synthetase deficiency

Reviewed December 2006

What is glutathione synthetase deficiency?

Glutathione synthetase deficiency is a disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.

Glutathione synthetase deficiency can be classified into three types: mild, moderate, and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). Rarely, affected people also excrete large amounts of a compound called 5-oxoproline in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells.

Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis).

In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections.

How common is glutathione synthetase deficiency?

Glutathione synthetase deficiency is very rare. This disorder has been described in about 70 people worldwide.

What genes are related to glutathione synthetase deficiency?

Mutations in the GSS gene cause glutathione synthetase deficiency.

The GSS gene provides instructions for making an enzyme called glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the body's cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency.

Related Gene(s)

Changes in this gene are associated with glutathione synthetase deficiency.

  • GSS

How do people inherit glutathione synthetase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of glutathione synthetase deficiency?

These resources address the diagnosis or management of glutathione synthetase deficiency and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/pyroglutamic-acidemia)
  • Genetic Testing Registry: Glutathione synthetase deficiency of erythrocytes, hemolytic anemia due to (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1856399)
  • Genetic Testing Registry: Gluthathione synthetase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0398746)

You might also find information on the diagnosis or management of glutathione synthetase deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about glutathione synthetase deficiency?

You may find the following resources about glutathione synthetase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for glutathione synthetase deficiency?

  • 5-oxoprolinemia
  • 5-oxoprolinuria
  • Deficiency of glutathione synthase
  • Deficiency of glutathione synthetase
  • pyroglutamic acidemia
  • pyroglutamic aciduria

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about glutathione synthetase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding glutathione synthetase deficiency?

acidity ; acidosis ; aciduria ; anemia ; ataxia ; autosomal ; autosomal recessive ; cancer ; cell ; compound ; deficiency ; disability ; DNA ; enzyme ; excrete ; gene ; glutathione ; hemolytic anemia ; inherited ; molecule ; neurological ; newborn screening ; oxygen ; psychomotor ; recessive ; screening

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Al-Jishi E, Meyer BF, Rashed MS, Al-Essa M, Al-Hamed MH, Sakati N, Sanjad S, Ozand PT, Kambouris M. Clinical, biochemical, and molecular characterization of patients with glutathione synthetase deficiency. Clin Genet. 1999 Jun;55(6):444-9. (http://www.ncbi.nlm.nih.gov/pubmed/10450861?dopt=Abstract)
  • Njålsson R, Norgren S. Physiological and pathological aspects of GSH metabolism. Acta Paediatr. 2005 Feb;94(2):132-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15981742?dopt=Abstract)
  • Njålsson R, Ristoff E, Carlsson K, Winkler A, Larsson A, Norgren S. Genotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency. Hum Genet. 2005 Apr;116(5):384-9. Epub 2005 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/15717202?dopt=Abstract)
  • Njålsson R. Glutathione synthetase deficiency. Cell Mol Life Sci. 2005 Sep;62(17):1938-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15990954?dopt=Abstract)
  • Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14988435?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2006
Published: December 22, 2014