Do you know someone with pyruvate kinase deficiency?”
First a bit of background: PK deficiency (PKD)is due to lack of (or mutant form of) one of the 4 isoforms of PK made by the cells. There are two PK genes and each gene produces two of the four isozymes of pyruvate kinase. Since this is a genetic disorder, it can be inherited – but there is only a little correlation between specific mutation and symptoms. In other words, a parent can have very minor symptoms and their child, if they inherit the mutation, could be quite ill (or vice versa). Obviously, there is a lot of influence from the metabolism of an individual. If symptoms are evident in neonates, these children typically have the most severe/life threatening forms of PKD – those with mild forms may not know it until adulthood or pregnancy. PK is important because it acts as a catalyst in the glycolysis pathway by which cells produce energy. A problem with any of the key components in glycolysis can alter the amount of energy produced. In the red blood cells, glycolysis is the only
Pyruvate Kinase Deficiency is an inherited autosomal recessive genetic disorder which affects the survival of red blood cells. 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, th
