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 hemoglobin- oxygen 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 Extra- Red Cell Commen ts Gly Hexokina 10q22 Ver Other colytic pathway se (HK) y rare isoenzymes known. Glucose 6-phosphate isomerase (G6PI) 19q31 .1 Rar e (4) N M, CNS Phosphof ructokinase (PFK) 12q13 Ver y rare My opathy Aldolase 16q22 -24 Ver y rare Triose phosphate isomerase (TPI) 12p13 Ver y rare CN S (severe), NM Glycerald 12p13 Ver My ehyde 3- phosphate dehydrogenase (GAPD) .31–p13.1 y rare opathy Diphosph oglycerate mutase (DPGM) 7q31- q34 Ver y rare Erythrocy tosis rather than hemolysis. Phosphog lycerate kinase (PGK) Xq13 Ver y rare CN S, NM May benefit from splenectomy. Pyruvate kinase (PK) 1q21 Rar e (2) May benefit from splenectomy. Red ox Glucose 6-phosphate dehydrogenase (G6PD) Xq28 Co mmon (1) Ve ry rarely granulocy tes In almost all cases only AHA from exogenous trigger. Glutathio ne synthase 20q11 .2 Ver y rare CN S γ- Glutamylcystein e synthase 6p12 Ver y rare CN S Cytochro me b5 reductase 22q13 .31–qter Rar e CN S Methemo globinemia rather than hemolysis. Nu cleotide metabolis m Adenylate kinase (AK) 9q34. 1 Ver y rare CN S Pyrimidin e 5'- nucleotidase 3q11– q12 Rar e (3) May benefit from (P5N) splenectomy. Note: CNS, central nervous system; AHA, acquired hemolytic anemia. . 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. 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. 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