Glutathione Synthetase Deficiency Medication
- Author: Darius J Adams, MD; Chief Editor: Luis O Rohena, MD more...
Treatment of individuals who have been diagnosed with glutathione synthetase (GS) deficiency involves providing supplements to correct the metabolic acidosis and supplying antioxidants such as vitamin E and vitamin C. NAC has been used in patients with glutathione synthetase deficiency because it is thought to increase the low intracellular glutathione concentrations and cysteine availability in the leukocytes of patients with this disorder. Use of sodium citrate and citric acid (Bicitra), vitamin C and vitamin E, thioctic acid (ie, lipoic acid), and NAC are included here.
Sodium bicarbonate is used as a gastric, systemic, and urinary alkalinizer and has been used in the treatment of acidosis resulting from metabolic and respiratory causes, including diabetic coma, diarrhea, kidney disturbances, and shock. Sodium bicarbonate also increases renal clearance of acidic drugs. Citric acid mixtures may also be used. With normal hepatic function, 1 mEq of citrate is converted to 1 mEq of bicarbonate.
PO medication useful in outpatient treatment of individuals with persistent acidosis. Each mL contains 1 mEq sodium ion and is equivalent to 1 mEq of bicarbonate. Also contains butylparaben, flavoring, and sodium saccharin. In certain situations, potassium citrate (as contained in Polycitra-K) may be preferable.
Palatability enhanced if chilled before swallowing.
Vitamins and antioxidants
These are organic substances required by the body in small amounts for various metabolic processes. Vitamins may be synthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation. They are used clinically for the prevention and treatment of specific vitamin deficiency states.
An antioxidant; one of the water-soluble vitamins.
An antioxidant; one of the fat-soluble vitamins.
Thioctic acid (Thiocid)
Also called alpha-lipoic acid. An antioxidant considered to be more effective than vitamin E or C in crossing the blood-brain barrier.
NAC is the N -acetyl derivative of the amino acid cysteine. NAC enhances the levels of glutathione in the liver, plasma, and bronchioalveolar lavage fluid. It is used to treat various diseases with the underlying etiology of decreased glutathione.
Has been used with GS deficiency because it is thought to increase low intracellular glutathione concentrations and cysteine availability in leukocytes.
Simon E, Vogel M, Fingerhut R, et al. Diagnosis of glutathione synthetase deficiency in newborn screening. J Inherit Metab Dis. 2009 Sep 2. [Medline].
Dahl N, Pigg M, Ristoff E, et al. Missense mutations in the human glutathione synthetase gene result in severe metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and neurological dysfunction. Hum Mol Genet. 1997 Jul. 6(7):1147-52. [Medline].
Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010 May. 6(5):274-85. [Medline].
Manning NJ, Davies NP, Olpin SE, et al. Prenatal diagnosis of glutathione synthase deficiency. Prenat Diagn. 1994 Jun. 14(6):475-8. [Medline].
Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug. 7(4):355-9. [Medline].
Boxer LA, Oliver JM, Spielberg SP, et al. Protection of granulocytes by vitamin E in glutathione synthetase deficiency. N Engl J Med. 1979 Oct 25. 301(17):901-5. [Medline].
Bruggemann LW, Groenendaal F, Ristoff E, et al. Glutathione synthetase deficiency associated with antenatal cerebral bleeding. J Inherit Metab Dis. 2004. 27(2):275-6. [Medline].
Divry P, Roulaud-Parrot F, Dorche C, et al. 5-Oxoprolinuria (glutathione synthetase deficiency): a case with neonatal presentation and rapid fatal outcome. J Inherit Metab Dis. 1991. 14(3):341-4. [Medline].
Erasmus E, Mienie LJ, de Vries WN, et al. Prenatal analysis in two suspected cases of glutathione synthetase deficiency. J Inherit Metab Dis. 1993. 16(5):837-43. [Medline].
Fily A, Vaillant C, Truffert P. [Gluthathion synthetase deficit in a newborn infant.]. Arch Pediatr. 2004 Nov. 11(11):1339-41. [Medline].
Jellum E, Kluge T, Borresen HC, et al. Pyroglutamic aciduria--a new inborn error of metabolism. Scand J Clin Lab Invest. 1970 Dec. 26(4):327-35. [Medline].
Larsson A, Zetterstrom R, Hagenfeldt L, et al. Pyroglutamic aciduria (5-oxoprolinuria), an inborn error in glutathione metabolism. Pediatr Res. 1974 Oct. 8(10):852-6. [Medline].
Marstein S, Jellum E, Halpern B. Biochemical studies of erythrocytes in a patient with pyroglutamic acidemia (5-oxoprolinemia). New Engl J Med. 1976. 295:
Martensson J, Gustafsson J, Larsson A. A therapeutic trial with N-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria). J Inherit Metab Dis. 1989. 12(2):120-30. [Medline].
Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983. 52:711-60. [Medline].
Mohler DN, Majerus PW, Minnich V, et al. Glutathione synthetase deficiency as a cause of hereditary hemolytic disease. N Engl J Med. 1970 Dec 3. 283(23):1253-7. [Medline].
Njalsson R, Carlsson K, Winkler A, et al. Diagnostics in patients with glutathione synthetase deficiency but without mutations in the exons of the GSS gene. Hum Mutat. 2003 Dec. 22(6):497. [Medline].
Ristoff E, Mayatepek E, Larsson A. Long-term clinical outcome in patients with glutathione synthetase deficiency. J Pediatr. 2001 Jul. 139(1):79-84. [Medline].
Robertson PL, Buchanan DN, Muenzer J. 5-Oxoprolinuria in an adolescent with chronic metabolic acidosis, mental retardation, and psychosis. J Pediatr. 1991 Jan. 118(1):92-5. [Medline].
Shi ZZ, Habib GM, Rhead WJ, et al. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. Nat Genet. 1996 Nov. 14(3):361-5. [Medline].
Spielberg SP, Boxer LA, Oliver JM, et al. Oxidative damage to neutrophils in glutathione synthetase deficiency. Br J Haematol. 1979 Jun. 42(2):215-23. [Medline].
Uhlig S, Wendel A. The physiological consequences of glutathione variations. Life Sci. 1992. 51(14):1083-94. [Medline].
Webb GC, Vaska VL, Gali RR, et al. The gene encoding human glutathione synthetase (GSS) maps to the long arm of chromosome 20 at band 11.2. Genomics. 1995 Dec 10. 30(3):617-9. [Medline].
Yapicioaylu H, Satar M, Tutak E. A newborn infant with generalized glutathione synthetase deficiency. Turk J Pediatr. 2004 Jan-Mar. 46(1):72-5. [Medline].