ble shape of the cell, which allows it to squeeze through narrow capillaries. The anemia observed in glycolytic enzyme deficien- cies is a consequence of the reduced rate of glycolysis, leading to decreased ATP production. The resulting alterations in the red blood cell membrane lead to changes in the shape of the cell and, ultimately, to phagocytosis by the cells of the reticuloendothelial system, particularly macrophages of the spleen. The premature death and lysis of red blood cells results in hemolytic anemia. Among patients exhibiting the rare genetic defects of glycolytic enzymes, about 95% show a deficiency in pyruvate kinase , and 4% exhibit phosphoglucose isomerase deficiency. PK deficiency is restricted to the erythrocytes, and produces mild to severe chronic hemolytic anemia (erythrocyte destruction), with the severe form requiring regular cell transfusions. The severity of the disease depends both on the degree of enzyme deficiency (gen- erally 5–25% of normal levels), and on the extent to which the individual’s red blood cells compensate by synthesizing increased levels of 2,3-BPG (see p. 31). Almost all individuals with PK defi- ciency have a mutant enzyme that shows abnormal properties— most often altered kinetics (Figure 8.20).