Glutathione Synthetase Deficiency Follow-up

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

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



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



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. Measurement of reduced glutathione synthetase activity can also be measured in fetal cells in the amniotic fluid.

In 1994, two pregnancies of two 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.

Today, prenatal counseling and testing is recommended for any family with a history of glutathione synthetase deficiency. In cases in which the two pathogenic mutations have already been identified in the affected individual, the at-risk pregnancy can then be tested via genetic mutation analysis. Preimplantation genetic diagnosis is also an option for these families. Carrier testing can also be offered to at-risk individuals so that risks to children can be determined.



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.