Spherocytic hemolytic anemia associated with glyceraldehyde 3 phosphate dehydrogenase deficiency

The red cells of a 43 yr old male with typical hereditary spherocytosis (HS), but with persistent post splenectomy reticulocytosis, were deficient in glyceraldehyde 3 phosphate dehydrogenase (G3PD). The red cells exhibited marked osmotic fragility and increased 48 hr autochemolysis in vitro (28%) which was almost totally corrected (3.5%) by glucose. Family history was strongly suggestive of autosomal dominant inheritance; the patient's father, 2 paternal uncles, 2 brothers and 1 sister have had repeated episodes of jaundice and were benefited by splenectomy. The patient's RBC membrane proteins, solubilized with sodium dodecyl sulfate, revealed on polyacrylemide gel electrophoresis almost total absence of band 6, previously identified by others as G3PD. G3PD measurements of leukocyte poor, whole blood hemolysates revealed approximately 50% activity; however, G3PD levels of isolated RBC ghosts had only 5 to 10% of normal activity. Similar studies on several splenectomized patients with classical hereditary spherocytosis and on normal controls yielded normal G3PD activities in hemolysates and stroma and unremarkable electrophoretic stromal protein patterns. These findings suggest that C3PD deficiency may result in a spherocytic hemolytic process essentially identical to hereditary spherocytosis by usual clinical and laboratory criteria. Alternatively, G3PD deficiency may be an incidental defect unrelated to hereditary spherocytosis; G3PD deficiency requires ES for phenotypic expression; or G3PD deficiency is a specific manifestation of this patient's type of HS, secondary to a defective membrane with decreased membrane bound enzyme and/or increased enzyme inactivation.