Glutathione Peroxidase Deficiency

Description

Several documented cases of glutathione peroxidase (GPX1; 138320) deficiency in association with hemolytic anemia have been reported. However, Paglia (1989) stated: 'To date, no defects in glutathione peroxidase have been unequivocally incriminated in the pathogenesis of hemolytic syndromes, although several instances of partial deficiency have been reported in patients with anemias of unknown etiology. This association may be coincidental, since there is a broad range of ethnic variation in the erythrocyte enzyme' (Beutler and Matsumoto, 1975).

Clinical Features

Necheles et al. (1968) observed hemolytic disease of the newborn with hyperbilirubinemia and Heinz bodies, associated with partial deficiency of red cell glutathione peroxidase. The clinical manifestations were self-limited; evidence of hemolysis had disappeared by 3 months of age, although the enzyme deficiency persisted. Sibs were affected in some instances and 1 parent had comparably depressed enzyme level and a history of neonatal jaundice.

Necheles et al. (1969) found low levels of glutathione peroxidase in an 18-year-old Puerto Rican male with compensated hemolytic anemia. Both parents and 1 sib had intermediate enzyme levels.

Perona et al. (1979) presented evidence that neonatal deficiency of the selenoenzyme glutathione peroxidase, with hematologic consequences, may result from 'selenium imbalance' during pregnancy. Glutathione peroxidase is involved in the detoxification of hydrogen peroxide. Selenium in the form of selenocysteine is part of its catalytic site. In experimental selenium deficiency in animals and in selenium deficiency that has developed in patients on long-term total parenteral alimentation, GSHPx activity in red blood cells, granulocytes, and platelets is low. Replacement with intravenous selenous acid results in slow recovery of GSHPx activity in red cells over a 3-month period; recovery occurs only in cells made in the presence of selenium (Cohen et al., 1985).

Cohen et al. (1989) studied 5 patients on long-term home parenteral nutrition who developed selenium and glutathione peroxidase deficiency. None had symptoms that could be attributed to the deficiencies or any change in their clinical course with Se supplementation and correction of the biochemical abnormalities.