Selective accumulation of cytosol CDP-choline as an isolated erythrocyte defect in chronic hemolysis.

Erythrocytes from a young woman with chronic hemolytic anemia were found to contain 0.31-0.45 mM CDP-choline, concentrations that are 15-25 times those in normal erythrocytes and equivalent to 20-30% of the total adenine nucleotide content. Accumulation of CDP-choline has been reported only in erythrocytes from subjects with severe (homozygous) pyrimidine nucleotidase deficiency. In the latter syndrome, however, pyrimidine nucleotidase activity is very low and a spectrum of uridine- and cytidine-containing nucleotides is present along with epiphenomena involving glutathione and ribosephosphate pyrophosphokinase. By contrast, selective accumulation of CDP-choline was the only abnormality demonstrable in proband erythrocytes. Membrane phospholipids were quantitatively and qualitatively normal, compatible with the observation that mature erythrocytes maintain membrane phospholipids largely by passive exchange with plasma components or by acylation of lysophospholipids. Although the presence of small amounts of other CDP-containing cofactors, such as CDP-ethanolamine, could not be entirely excluded, the cytidine/choline ratio closely approximated 1:1 in all studies. These data are compatible with the view that choline phosphotransferase and ethanolamine phosphotransferase are separate enzymes in erythroid cells. Selective accumulation of CDP-choline in proband erythrocytes is also compatible with an inherited deficiency of choline phosphotransferase in erythroid precursors, though this hypothesis remains unproved.