Glutathione Synthetase Deficiency Workup

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

Laboratory Studies

See the list below:

  • Electrolyte and blood gas determinations indicate high anion gap metabolic acidosis. The CBC count demonstrates hemolytic anemia. Diagnosis of glutathione synthetase (GS) deficiency is confirmed by the presence of a large peak of 5-oxoproline in the urine. Concentrations of this metabolite are also increased in the cerebrospinal fluid (CSF) and blood. Diagnosis can be confirmed through enzyme analysis of glutathione synthetase (which is found to be deficient) in cultured skin fibroblasts. Upon routine testing, in addition to a hemolytic anemia, episodic neutropenia may occur. Additional findings include the following:
    • Neutrophil bactericidal and iodination defects, which are corrected with vitamin E therapy
    • Pyroglutamic aciduria
    • Pyroglutamic acidemia
    • Decreased glutathione in erythrocytes
    • Increased gamma-glutamylcysteine synthetase
  • Moderate and severe forms cannot be differentiated based on enzyme activity, which suggests that other factors are involved in the final phenotypic presentation.
  • Molecular sequencing of the GSS gene can be performed to assist in confirming the diagnosis and for providing accurate recurrence risks to family members.
Contributor Information and Disclosures

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.


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.

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Biochemical pathway of glutathione synthetase.
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