eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Glutathione Synthetase Deficiency: Follow-up

Author: Darius J Adams, MD, Assistant Professor, Department of Pediatrics, Section of Genetics and Metabolism, Albany Medical Center
Coauthor(s): Melissa P Wasserstein, MD, Associate Professor, Departments of Genetics and Genomic Sciences and Pediatrics, Mount Sinai School of Medicine
Contributor Information and Disclosures

Updated: Oct 14, 2009

Follow-up

Further Outpatient Care

  • 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.

Transfer

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

Deterrence/Prevention

  • 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.2 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.

Prognosis

  • 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.

Miscellaneous

Medicolegal Pitfalls

  • Severe high anion gap metabolic acidosis may be attributed to poisoning. The laboratory diagnosis of this condition is nontrivial and requires ordering the correct test (ie, urine organic acids). Laboratory personnel with experience in detecting 5-oxoproline should perform this test.
 


More on Glutathione Synthetase Deficiency

Overview: Glutathione Synthetase Deficiency
Differential Diagnoses & Workup: Glutathione Synthetase Deficiency
Treatment & Medication: Glutathione Synthetase Deficiency
Follow-up: Glutathione Synthetase Deficiency
Multimedia: Glutathione Synthetase Deficiency
References
[ CLOSE WINDOW ]

References

  1. 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. Jul 1997;6(7):1147-52. [Medline].

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

  3. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. Aug 2007;7(4):355-9. [Medline].

  4. Boxer LA, Oliver JM, Spielberg SP, et al. Protection of granulocytes by vitamin E in glutathione synthetase deficiency. N Engl J Med. Oct 25 1979;301(17):901-5. [Medline].

  5. 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].

  6. 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].

  7. 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].

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

  9. Jellum E, Kluge T, Borresen HC, et al. Pyroglutamic aciduria--a new inborn error of metabolism. Scand J Clin Lab Invest. Dec 1970;26(4):327-35. [Medline].

  10. Larsson A, Zetterstrom R, Hagenfeldt L, et al. Pyroglutamic aciduria (5-oxoprolinuria), an inborn error in glutathione metabolism. Pediatr Res. Oct 1974;8(10):852-6. [Medline].

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

  12. 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].

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

  14. Mohler DN, Majerus PW, Minnich V, et al. Glutathione synthetase deficiency as a cause of hereditary hemolytic disease. N Engl J Med. Dec 3 1970;283(23):1253-7. [Medline].

  15. 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. Dec 2003;22(6):497. [Medline].

  16. Ristoff E, Mayatepek E, Larsson A. Long-term clinical outcome in patients with glutathione synthetase deficiency. J Pediatr. Jul 2001;139(1):79-84. [Medline].

  17. Robertson PL, Buchanan DN, Muenzer J. 5-Oxoprolinuria in an adolescent with chronic metabolic acidosis, mental retardation, and psychosis. J Pediatr. Jan 1991;118(1):92-5. [Medline].

  18. Shi ZZ, Habib GM, Rhead WJ, et al. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. Nat Genet. Nov 1996;14(3):361-5. [Medline].

  19. Spielberg SP, Boxer LA, Oliver JM, et al. Oxidative damage to neutrophils in glutathione synthetase deficiency. Br J Haematol. Jun 1979;42(2):215-23. [Medline].

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

  21. 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. Dec 10 1995;30(3):617-9. [Medline].

  22. Yapicioaylu H, Satar M, Tutak E. A newborn infant with generalized glutathione synthetase deficiency. Turk J Pediatr. Jan-Mar 2004;46(1):72-5. [Medline].

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

glutathione synthetase deficiency, GS deficiency, 5-oxoprolinemia, 5-oxoprolinuria, pyroglutamicaciduria, pyroglutamic aciduria, pyroglutamic acidemia, high anion gap metabolic acidosis, severe metabolic acidosis, chronic metabolic acidosis, hemolytic anemia, enzyme deficiency, glutathione, neutropenia, GSS, GSHS, inborn error of glutathione metabolism, ataxia, dysarthria, tremors, psychotic behavior

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Darius J Adams, MD, Assistant Professor, Department of Pediatrics, Section of Genetics and Metabolism, Albany Medical Center
Darius J Adams, MD is a member of the following medical societies: American Academy of Pediatrics
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.

Medical Editor

Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director: Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA).
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, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research
Disclosure: Genzyme Honoraria Speaking and teaching; Genzyme Grant/research funds Other; Shire Honoraria Speaking and teaching; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Speaking and teaching; Biomarin Consulting fee Consulting; Amicus  Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leonard G Feld, MD, PhD, MMM, FAAP, Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center
Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.