Glutathione Synthetase Deficiency Workup

Updated: May 18, 2017
  • Author: Reem Saadeh-Haddad, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Laboratory Studies

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.

Enzyme assay will show decreased activity of the enzyme glutathione synthetase in erythrocytes or cultured fibroblasts. Moderate and severe forms cannot be differentiated based on enzyme activity, which suggests that other factors are involved in the final phenotypic presentation.

Urine organic acids will show increased 5-oxoproline levels.

Molecular sequencing of the GSS gene can be performed to assist in confirming the diagnosis and for providing accurate recurrence risks to family members.