Pyruvate kinase deficiency

Overview
Pyruvate Kinase Deficiency is an inherited autosomal recessive genetic disorder which affects the survival of red blood cells. A variety of mutations can lead to lowered production, activity, or stability of pyruvate kinase, an enzyme essential to glycolysis. A total lack of this enzyme's activity will be lethal. Because the ability of erythrocytes to manufacture ATP depends on glycolysis, the cells become deficient in energy and unable to maintain the activity of the basolateral Na+/K+-ATPase. This will result in an increase in intracellular [Na+] which will cause water to diffuse passively into the red blood cell (RBC) and will lead to swelling. This swelling will lead to lysis of the RBCs and an increase in plasma bilirubin. The increase in plasma bilirubin will lead to jaundice and the lysis of the RBCs will lead to hemolytic anemia. The buildup of reaction intermediates can also increase the level of 2,3-bisphosphoglycerate in the cells and affect tissue oxygenation. This will cause a "right shift" in the hemoglobin oxygen saturation curve, implying a decreased oxygen affinity for the hemoglobin and earlier oxygen unloading than under normal conditions.

Clincally, this disorder is most common glycolytic enzyme deficiency, that will lead to hemolytic anemia.

Most affected individuals do not require treatment. Individuals who are most severely affected may die in utero of anemia or may require blood transfusions or splenectomy, but most of the symptomatology is limited to early life and times of physiologic stress or infection.

Red blood cells use glycolysis as their sole energy source. In pyruvate kinase deficiency, the last step (phosphoenolpyruvate converted to pyruvate) of glycolsis is unable to occur. A discrepancy between red blood cell energy requirements and ATP generating capacity produces irreversible membrane injury resulting in cellular distortion, rigidity, and dehydration. This leads to premature erythrocyte destruction by the spleen and liver.

Treatment
Treatment can include a blood transfusion or removal of the spleen. Treatment is usually effective in reducing the severity of the symptoms.