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Gamma-glutamylcysteine synthetase deficiency has been detected in nine patients from seven families worldwide.

Gamma-glutamylcysteine synthetase catalyses the first and rate-limiting step in the synthesis of glutathione. Its deficiency results in low cellular levels of glutathione and gamma-glutamylcysteine. Four different mutations in the heavy subunit have been identified in four families affected by gamma-glutamylcysteine synthetase deficiency.

The diagnosis consists of the following stages: clinical findings, the finding of low cellular levels of glutathione, low activity of gamma-glutamylcysteine synthetase, and mutation analysis of the gamma-glutamylcysteine synthetase genes.

The differential diagnosis should include glutathione synthetase deficiency (see this term), which is also associated with low levels of glutathione.

Antenatal diagnosis could be performed by measurement of gamma-glutamylcysteine synthetase activity or mutational analysis (if the mutation in the family is known) of chorionic villi samples or cultured amniocytes.

As transmission is autosomal recessive, families should be referred for genetic counselling.

Patients with gamma-glutamylcysteine synthetase deficiency should avoid drugs known to precipitate hemolytic crises in patients with glucose-6-phosphate dehydrogenase deficiency, e.g. phenobarbital, acetylsalicylic acid and sulfonamides. It is possible that patients would benefit from treatment with anti-oxidants but no studies have been made.

The prognosis is difficult to predict, as only nine patients are known worldwide.