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).

This is a form of nonspherocytic hemolytic anemia of Dacie type I (in vitro autohemolysis is not corrected by added glucose). After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies; 208530).

Congenital nonspherocytic hemolytic anemia-1 (CNSHA1), caused by mutation in the G6PD gene, is the most common genetic form of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans. Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (see 611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (summary by Cappellini and Fiorelli, 2008).