title: Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary glutathione synthetase deficiency.
abstract: A 45-month-old girl with 5-oxoprolinuria (pyroglutamic aciduria), hemolysis, and marked glutathione depletion caused by deficiency of glutathione synthetase was followed before and during treatment with ascorbate or N-acetylcysteine. High doses of ascorbate (0.7 mmol/kg per day) or N-acetylcysteine (6 mmol/kg per day) were given for 1 to 2 weeks without any obvious deleterious side effects. Ascorbate markedly increased lymphocyte (4-fold) and plasma (8-fold) levels of glutathione. N-Acetylcysteine also increased lymphocyte (3.5-fold) and plasma (6-fold) levels of glutathione. After these treatments were discontinued, lymphocyte and plasma glutathione levels decreased rapidly to pretreatment levels. Ascorbate treatment was extended for 1 year, and lymphocyte (4-fold) and plasma (2- to 5-fold) glutathione levels remained elevated above baseline. In parallel, the hematocrit increased from 25.4% to 32.6%, and the reticulocyte count decreased from 11% to 4%. The results demonstrate that ascorbate and N-acetylcysteine can decrease erythrocyte turnover in patients with hereditary glutathione deficiency by increasing glutathione levels.
authors.affiliation: Department of Internal Medicine, Greenwich Hospital/Yale University School of Medicine, CT 06830-4697.
authors.forename: A
authors.initials: A
authors.lastname: Jain
authors.forename: N R
authors.initials: NR
authors.lastname: Buist
authors.forename: N G
authors.initials: NG
authors.lastname: Kennaway
authors.forename: B R
authors.initials: BR
authors.lastname: Powell
authors.forename: P A
authors.initials: PA
authors.lastname: Auld
authors.forename: J
authors.initials: J
authors.lastname: Mårtensson
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D005981:Glutathione Synthase / Q000032:analysis / Q000097:blood / Q000172:deficiency*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D014810:Vitamin E; D005981:Glutathione Synthase; D001205:Ascorbic Acid; D000111:Acetylcysteine