Selective reticulocyte destruction in erythrocyte pyruvate kinase deficiency

A B S T R A C T Radioisotope studies of bilirubin turn- over, ferrokinetics, and red cell survival ('Cr) in a patient with erythrocyte PK deficiency have provided evidence for prompt reticulocyte sequestration and destruction by the reticuloendothelial system. More ma- ture erythrocytes appeared to survive well despite their deficiency of PK. PK-deficient reticulocytes, dependent upon oxidative phosphorylation for ATP production, are exquisitely sensitive to cyanide-or nitrogen-induced mitochondrial inhibition. If oxidative phosphorylation is unavailable, ATP levels decline rapidly, producing alter- ations in the cell membrane which allow massive losses of potassium and water. The result is a shrunken, spicu- lated, viscous cell whose rheologic properties would favor its sequestration by the reticuloendothelial sys- tem. Those reticulocytes with particularly low levels of PK exhibit very low glycolytic rates and thus are uniquely reliant upon oxidative phosphorylation. Other reticulocytes, better endowed with PK activity, can meet the increased ATP requirements of young erythrocytes. Upon reaching maturity, such cells have diminished ATP needs and can, therefore, survive despite their enzyme deficiency. * Values are those found for normal adults in our laboratory. Normal values cited for bilirubin turnover were obtained in 19 normal individuals studied at the National Cancer Institute by Dr. Joseph Bloomer and his coworkers. (Personal communication.