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Glutathione Synthetase Deficiency Follow-up

  • Author: Darius J Adams, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Nov 17, 2014
 

Further Outpatient Care

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  • Glutathione synthetase (GS) deficiency is a chronic life-threatening disorder. Regular follow-up with a metabolic diseases specialist may be indicated. All patients should be encouraged to wear a medical alert bracelet or necklace.
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Transfer

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  • Transfer to a center where metabolic diseases specialists are available may be indicated.
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Deterrence/Prevention

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  • Because accumulation of 5-oxoproline occurs in all body fluids, especially the urine, of affected individuals, the possibility of prenatal diagnosis with amniotic fluid was realized; most of this fluid is from fetal urine after the first trimester.
  • In 1994, 2 pregnancies of 2 at-risk couples were studied at 16 weeks' gestation.[4] In both cases, the levels of 5-oxoproline were 25-30 times reference range values. Both pregnancies were terminated, and the diagnosis was confirmed in one case by cultured fetal fibroblast enzyme analysis.
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Prognosis

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  • In the systemic form, chronic metabolic acidosis must be treated, but long-term prognosis is guarded. The lack of glutathione in erythrocytes alone is apparently tolerable, as has been noted with the peripheral form of this condition; however, in severe glutathione synthetase, a progressive loss of function occurs, leading to severe mental retardation, ataxia, and seizure disorders.
  • The oldest reported survivor of severe glutathione synthetase was aged 24 years and had experienced significant neurological deterioration over the previous few years. Older children with mild and moderate forms who are doing well have been reported.
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Contributor Information and Disclosures
Author

Darius J Adams, MD Director, Personalized Genomic Medicine, Atlantic Health System; Director, Division of Genetics and Metabolism, Goryeb Children's Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Melissa P Wasserstein, MD Associate Professor, Departments of Genetics and Genomic Sciences and Pediatrics, Mount Sinai School of Medicine

Melissa P Wasserstein, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

References
  1. Simon E, Vogel M, Fingerhut R, et al. Diagnosis of glutathione synthetase deficiency in newborn screening. J Inherit Metab Dis. 2009 Sep 2. [Medline].

  2. 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].

  3. Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010 May. 6(5):274-85. [Medline].

  4. Manning NJ, Davies NP, Olpin SE, et al. Prenatal diagnosis of glutathione synthase deficiency. Prenat Diagn. 1994 Jun. 14(6):475-8. [Medline].

  5. 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].

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. Fily A, Vaillant C, Truffert P. [Gluthathion synthetase deficit in a newborn infant.]. Arch Pediatr. 2004 Nov. 11(11):1339-41. [Medline].

  11. 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].

  12. 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].

  13. Marstein S, Jellum E, Halpern B. Biochemical studies of erythrocytes in a patient with pyroglutamic acidemia (5-oxoprolinemia). New Engl J Med. 1976. 295:

  14. 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].

  15. Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983. 52:711-60. [Medline].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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].

  21. 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].

  22. Uhlig S, Wendel A. The physiological consequences of glutathione variations. Life Sci. 1992. 51(14):1083-94. [Medline].

  23. 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].

  24. 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].

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Biochemical pathway of glutathione synthetase.
 
 
 
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