Gamma-glutamylcysteine synthetase deficiency
Incidence
Gamma-glutamylcysteine synthetase deficiency is a very rare autosomal recessive disease. More than 10 patients in 7 families are known worldwide.
Clinical Characteristics
Gamma-glutamylcysteine synthetase deficiency is a rare autosomal recessive disease detected in more than 10 patients in 7 families worldwide. The most prominent symptom is hemolytic anemia but neurological symptoms have also been reported. All patients with Gamma-glutamylcysteine synthetase deficiency have had hemolytic anemia, rather mild usually. In addition two siblings also had cerebellar involvement, neuropathy, myopathy and aminoaciduria. One patient was reported to have learning disability with dyslexia and was also thought to be mentally retarded. It remains to be established whether CNS symptoms reported in some patients with gamma-glutamylcysteine synthetase are related to the enzyme defect or not. Gamma-glutamylcysteine synthetase catalyses the first step in the synthesis of glutathione. Its deficiency results in low cellular levels of glutathione and gamma-glutamylcysteine. The diagnosis is composed of the following stages: clinical findings, the finding of low levels of glutathione and gamma-glutamylcysteine synthetase, and mutation analysis of the gamma-glutamylcysteine synthetase genes. 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, sulfonamides.
Precipitants
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, sulfonamides.
Provocation Tests
Any drug that affects G6PD may induce hemolitic anemia. Not recommended.
Diagnostic Procedures
EB-R, EB-F. GSH in erythrocytes can be measured with the 5,5'-dithiobis(2-nitrobenzoic acid)GSH recycling assay, and GSH in fibroblasts with HPLC. gamma-Glutamylcysteine synthetase in erythrocytes and/or cultured fibroblasts can be measured.