Glutathione Reductase

Alternative Names

  • GSR
  • Glutathione Reductase, Hemolytic Anemia due to Deficiency of, in Red Cells
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WHO-ICD-10 version:2010

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Haemolytic anaemias

OMIM Number

138300

Mode of Inheritance

Autosomal recessive

Gene Map Locus

8p12

Description

The enzyme encoded by the GSR gene is called glutathione reductase (GR) also known as glutathione-disulfide reductase (GSR), a homodimeric flavoprotein.  This enzyme is critical molecule in protecting hemoglobin, red cell enzymes, and biological cell membranes against oxidative stress by increasing the level of reduced glutathione (GSSGR) in the process of aerobic glycolysis; it catalyzes the reduction of glutathione disulfide (GSSG) to the sulfhydryl form glutathione (GSH).  It also functions as dimeric disulfide oxidoreductase and utilizes an FAD prosthetic group and NADPH to reduce one molar equivalent of GSSG to two molar equivalents of GSH.  Defects in this enzyme result in mild to moderately severe hemolytic anemia upon exposure to certain drugs or chemicals.  Haemolytic anaemia due to glutathione reductase (GSR) deficiency is extremely rare, characterized by nearly complete absence of GSR activity in erythrocytes.  Transmission is autosomal recessive.  This disease should be distinguished from glutathione reductase deficiency secondary to dietary riboflavin deficiency and from the acute pharmacologic phenocopy induced by the alkylating agent Carmustine (BCNU) that is used in chemotherapy.

Molecular Genetics

The gene GSR is located on chromosome 8p21.1 and consists of 13 exons spanning approximately 50 kb. It has two in-frame start codons that are thought to initiate the synthesis of mitochondrial and cytosolic GR. Mutations within this gene are the cause of hereditary glutathione reductase deficiency.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

el-Hazmi & Warsy (1989) conducted a study among 461 Saudis to determine GR deficiency due to GR mutations and acquired causes.  Red cell GR activity was evaluated in males and females from the South-Western province of Saudi Arabia.  The frequency of GR deficiency was 24.5% in males and 20.3% in females, while the frequency of acquired riboflavin deficiency was 17.8% in males and 22.4% in females. 

During the period from 1984 to 1990, Warsy and el-Hazmi (1999) conducted a study on 1691 Saudis to determine the overall frequency of GR deficiency and to identify whether the deficiency is due to genetic defect or resulted from a nutritional deficiency of riboflavin.  If the GR was corrected in the presence of FAD, it was classified as a nutritional deficiency, if not then it was classified as a genetic deficiency.  A total of 207 individuals (132 male and 75 females) had GR deficiency that is genetic, and 330 individuals (180 male and 150 females) had GR deficiency due to riboflavin deficiency.  The greatest prevalence of genetically determined GR deficiency was found in Gizan, followed by Al-Hafouf in Eastern Province of the country.

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