Disorders of the hexose monophosphate shunt and glutathione metabolism other than glucose-6-phosphate dehydrogenase deficiency
- Bertil Glader, MD, PhD
Bertil Glader, MD, PhD
- Professor of Pediatrics
- Stanford University School of Medicine
The red blood cell is protected from oxidant injury via enzymes of the hexose monophosphate (HMP) shunt pathway and those of the glutathione synthetic and metabolic pathways (figure 1 and figure 2). The most common abnormality in this system is glucose-6-phosphate dehydrogenase deficiency, which can lead to varying degrees of hemolysis. This disorder is discussed in depth separately. (See "Genetics and pathophysiology of glucose-6-phosphate dehydrogenase deficiency" and "Clinical manifestations of glucose-6-phosphate dehydrogenase deficiency" and "Diagnosis and treatment of glucose-6-phosphate dehydrogenase deficiency".)
Abnormalities have been reported in several of the other enzymes in these two pathways, some of which are associated with increased red cell destruction (hemolysis). These disorders will be reviewed here.
RED CELL CHANGES IN OXIDANT STATES
When disorders of the hexose monophosphate shunt and glutathione metabolism result in anemia, this happens because of oxidant damage to circulating red cells with resultant decreased survival (ie, increased hemolysis), with the following changes.
●Biochemical – Increased hemolysis is associated with increases in indirect bilirubin and lactate dehydrogenase and reductions in haptoglobin, and is usually accompanied by an abrupt fall in hemoglobin if hemolysis is severe. If intravascular hemolysis is present, there will be hemoglobinuria, dark urine, and the presence of hemosiderin-laden cells in the urine sediment.
●Red cell changes – Red cell changes in oxidant-related hemolysis include the presence of microspherocytes, red cell fragments, and eccentrocytes or "bite cells" (picture 1). Special stains document the production of Heinz bodies, which are collections of denatured globin chains often attached to the red cell membrane. If and when the bone marrow responds to the acute anemia, there will be an increase in reticulocytes.
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- RED CELL CHANGES IN OXIDANT STATES
- 6-PHOSPHOGLUCONATE DEHYDROGENASE DEFICIENCY
- GLUTATHIONE REDUCTASE DEFICIENCY
- Acquired deficiency
- - Nutritional
- - Drug-induced
- Genetically determined deficiency
- GLUTATHIONE PEROXIDASE DEFICIENCY
- DEFECTS IN GLUTATHIONE SYNTHESIS
- Gamma-glutamyl-cysteine synthetase deficiency
- Glutathione synthetase deficiency
- - Management
- GLUTATHIONE S-TRANSFERASE DEFICIENCY
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