Glutathione Synthetase Deficiency Treatment & Management

  • Author: Darius J Adams, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 2, 2012
 

Medical Care

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.[3] A combination of sodium citrate and citric acid (Bicitra) may be used as an oral medication and can maintain plasma bicarbonate levels within the reference range. Alternatively, bicarbonate may be used; however, very large doses may be needed.

  • The prognosis for glutathione synthetase deficiency widely varies. In some cases, early use of sodium citrate and citric acid (Bicitra) or other buffers, vitamin C, and vitamin E may allow normal development to occur.
  • Experiments using lipoic acid as an intracerebral antioxidant have been performed in animal models. Lipoic acid penetrates the blood-brain barrier well and may prevent the onset of learning disabilities in children with glutathione synthetase deficiency. However, individuals may have an absolute requirement of glutathione for the production of certain leukotrienes and possibly even neurotransmitters. If this is the case, lipoic acid may not effectively correct the problem.
  • N -acetylcysteine (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 these patients. Whether these findings in leukocytes may result in similar changes in neurons is not yet known.
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Consultations

  • Consultations with a clinical biochemical geneticist, metabolic diseases specialist, or hematologist may be indicated.
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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.

Specialty Editor Board

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research, Professor of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Faculty, Program in Molecular and Cellular Biosciences, Oregon Health and Science University School of Medicine; Attending Physician, Doernbecher Children's Hospital; Staff Consultant, Director of Metabolic Bone Disease Clinic, Shriners Hospital Portland

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: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

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.

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.

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 and Genetics, Director RSA, 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.

References

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

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  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].

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Biochemical pathway of glutathione synthetase.
 
 
 
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