Glutathione synthetase deficiency

What causes glutathione synthetase deficiency?

Glutathione synthetase deficiency is caused by changes (pathogenic variants or mutations) in the _GSS _gene. This gene provides instructions to the body for making an enzyme called glutathione synthetase. Glutathione synthetase is one of the enzymes that helps the body make a molecule called glutathione. Glutathione is important because it is an antioxidant, meaning it helps prevent damage in the cells of the body. Many normal processes in the cells can create substances that cause damage to the cell if the substances are not removed. Glutathione helps change (neutralize) these damaging substances into harmless substances. It also neutralizes other substances that can cause damage to cells such as medications. Glutathione is also part of the process that helps break down a substance called 5-oxoproline.

People with pathogenic variants in the GSS gene do not have enough working glutathione synthetase, and therefore their cells do not have enough glutathione to neutralize harmful substances or to break down 5-oxoproline. This causes 5-oxoproline to build up in the body. When 5-oxoproline builds up in the body, it causes the symptoms of glutathione synthetase deficiency.

Because there are mild, moderate, and severe forms of glutathione synthetase deficiency, it is thought that there may be other environmental and genetic factors that may impact the severity of symptoms associated with the deficiency.

Last updated on 05-01-20

How is glutathione synthetase deficiency diagnosed?

A diagnosis of glutathione synthetase deficiency may be suspected when a person has problems associated with the deficiency such as metabolic acidosis. Metabolic acidosis is suggestive of a metabolic disorder including glutathione synthetase deficiency. A doctor may then order tests to determine the exact cause of the medical problems. These tests may include an enzyme assay, which is a test that determines if the enzymes of the body are working as they should. A doctor may also order a blood test and urinalysis to determine if the levels of certain substances in the blood and urine are within the normal range. If these tests suggest glutathione synthetase deficiency, a doctor may order genetic testing of the GSS gene to confirm the diagnosis.

Last updated on 05-01-20

How is glutathione synthetase deficiency inherited?

Glutathione synthetase deficiency is inherited in an autosomal recessive manner. Like most genes, the GSS gene comes in a pair (2 copies). One copy of the gene comes from the mother and one from the father. Autosomal recessive means that both copies of the GSS __ gene must have a disease-causing change (pathogenic variant or mutation) for people to have glutathione synthetase deficiency. A person with only one changed copy of the GSS gene is called a carrier of glutathione synthetase deficiency. Carriers do not usually have signs and symptoms of glutathione synthetase deficiency. When two carriers of glutathione synthetase deficiency have children together, for each child there is a:

  • 25% chance to inherit both changed copies of the GSS gene, meaning the child will have glutathione synthetase deficiency
  • 50% chance to inherit one changed copy of the GSS gene, meaning the child will be a carrier of glutathione synthetase deficiency like both parents
  • 25% chance to inherit both working copies of the GSS gene, meaning the child will not have glutathione synthetase deficiency and will not be a carrier of the deficiency

Last updated on 05-01-20

What is the long-term outlook for people with glutathione synthetase deficiency?

The long-term outlook for people with glutathione synthetase deficiency depends on whether the person has the mild, moderate, or severe form of the deficiency. Unfortunately, the severe form of glutathione synthetase deficiency may affect the brain (neurological problems) and may get worse as the child grows older (progressive). This can cause people with the severe form of the deficiency to have intellectual disability, seizures, and behavioral abnormalities that may worsen with time. Some people with the severe form of the deficiency have been reported to live until early adulthood. In some cases, treatment may help improve the long-term outlook for people with the severe form of the deficiency.

The mild and moderate forms of glutathione synthetase deficiency usually have a better long-term outlook. Symptoms such as metabolic acidosis often become more manageable as a person with the deficiency gets older.

Last updated on 05-01-20

How might glutathione synthetase deficiency be treated?

Unfortunately, there is no cure for glutathione synthetase deficiency. Treatment typically includes managing the medical problems associated with the deficiency. For example, if a person with glutathione synthetase deficiency develops metabolic acidosis, sodium bicarbonate can be used to treat the symptoms. Sodium bicarbonate may be given through an injection in the veins (intravenously). People with glutathione synthetase deficiency may also be recommended to take supplements for vitamin E and vitamin C. These vitamins are known as antioxidants. Antioxidants help the body neutralize some of the byproducts of chemical reactions that can be damaging to cells of the body, which is one of the roles of glutathione. In some cases, doctors may recommend a combination of sodium citrate and citric acid as medication to help treat people with glutathione synthetase deficiency. People with the deficiency may be recommended to avoid medications that can cause a more rapid breakdown of red blood cells (hemolytic anemia).

People with glutathione synthetase deficiency require close follow-up by doctors who are familiar with the deficiency. Therefore, a consultation with genetics specialists such as a biochemical geneticist, metabolic disorders specialist, and genetic counselor, are recommended for the parents of children with glutathione synthetase deficiency.

Last updated on 05-01-20

Where To Start

5-oxoprolinuria

The Merck Manual provides information on metabolic acidosis. Click on Merck Manual to view this information page.

Last updated on 04-27-20

Name: Metabolic Support UK 5 Hilliards Court Sandpiper Way
Chester Business Park
Chester, CH4 9QP, United Kingdom
Phone: 0845 241 2173 Toll Free: 0800 652 3181 Email: https://www.metabolicsupportuk.org/contact-us Url: https://www.metabolicsupportuk.org
Name: Organic Acidemia Association 9040 Duluth Street
Golden Valley, MN, 55427, United States
Phone: 763-559-1797 Fax : 866-539-4060 Email: mkstagni@gmail.com Url: http://www.oaanews.org/
Name: Genetic Metabolic Dietitians International P.O. Box 1462
Hillsborough, NC, 27278, United States
Email: info@gdmi.org Url: http://www.gmdi.org/

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