Glutathione Synthetase Deficiency as a Cause of Hereditary Hemolytic Disease

Two enzymes are required for de novo glutathione synthesis: glutamyl-cysteine synthetase and glutathione synthetase. In a 32-year-old man with a well compensated hemolytic disorder, the erythrocytes were devoid of glutathione synthetase activity, whereas erythrocytes from his parents and four children had levels that were half those of normal control erythrocytes. These heterozygotes had no other detectable hematologic abnormalities. Both the patient and his heterozygous relatives had normal levels of erythrocyte glutamyl-cysteine synthetase. Glutathione synthetase deficiency is an autosomally inherited trait that, in a homozygous subject, produces a mild hemolytic disorder.