Abnormalities of the Glycolytic Pathway (Fig. 101-1) Since red cells, in the course of their differentiation, have sacrificed not only their nucleus and their ribosomes but also their mitochondria, they rely exclusively on the anaerobic portion of the glycolytic pathway for producing energy in the form of ATP. Most of the ATP is required by the red cell for cation transport against a concentration gradient across the membrane. If this fails, due to a defect of any of the enzymes of the glycolytic pathway, the result will be hemolytic disease. Pyruvate Kinase Deficiency Abnormalities of the glycolytic pathway are all inherited. | Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss Part 8 Abnormalities of the Glycolytic Pathway Fig. 101-1 Since red cells in the course of their differentiation have sacrificed not only their nucleus and their ribosomes but also their mitochondria they rely exclusively on the anaerobic portion of the glycolytic pathway for producing energy in the form of ATP. Most of the ATP is required by the red cell for cation transport against a concentration gradient across the membrane. If this fails due to a defect of any of the enzymes of the glycolytic pathway the result will be hemolytic disease. Pyruvate Kinase Deficiency Abnormalities of the glycolytic pathway are all inherited and all rare Table 101-4 . Among them deficiency of pyruvate kinase PK is the least rare with an estimated prevalence of 1 10 000. The clinical picture is that of an HA that often presents in the newborn with neonatal jaundice the jaundice persists and is usually associated with a very high reticulocytosis. The anemia is of variable severity sometimes it is so severe as to require regular blood transfusions sometimes it is mild bordering on a nearly compensated hemolytic disorder. As a result the diagnosis may be delayed and in some cases it is made in young adults for instance in a woman during her first pregnancy when the anemia may get worse. In part the delay in diagnosis is due to the fact that the anemia is remarkably well-tolerated because the metabolic block at the last step in glycolysis causes an increase in bisphosphoglycerate or DPG a major effector of the hemoglobinoxygen dissociation curve. Thus the oxygen delivery to the tissues is increased. Table 101-4 Red Cell Enzyme Abnormalities Causing Hemolysis Enzyme Acronym Chro mosomal Location Pre valence of Enzyme Deficiency Rank Cli nical Manifest ations ExtraRed Cell Commen ts Gly Hexokina 10q22 Ver Other colytic pathway se HK y rare isoenzymes known. Glucose 6-phosphate isomerase G6PIJ 19q31 .1 Rar e 4 N M CNS .
