Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells.

Paroxysmal nocturnal hemoglobinuria them had the B variant of this enzyme (PNH) was diagnosed in a 26-year-old (as expected in female subjects heterozy-Nigerian woman who subsequently died gous at this sex-linked locus). The red of amebic colitis. The patient's red cells cells bearing the PNH abnormality only exhibited mosaicism with respect to glu-had the B variant, suggesting that they cose 6-phosphate dehydrogenase, in that all belonged to a single abnormal clone. some of them had the A, and some of I N CONTRAST to the other hemolytic disorders associated with an intrinsic defect of the erythrocyte, paroxysmal nocturnal hemoglobinuria (PNH) is not a genetically determined disease (evidence reviewed by Crosby1; Dacie2). Accordingly, it has been suggested that the erythrocyte population with the PNH abnormality may consist of a clone of cells which arose by somatic mutation .3'4 Here we present experimental support for this idea. We found that in a patient suffering from PNH, and who exhibited erythrocyte mosaicism with respect to glucose 6-phosphate dehydrogenase,5 all the red cells carrying the PNH abnormality were homogeneous with respect to that marker. The data were obtained while studying a patient with PNH (a condition not yet described in tropical Africa), who also illustrates an exceptional complication of the disease, unfortunately fatal in our case: fulminating amebic colitis. METHODS Routine hematologic investigations were carried out by standard technics.6'T The acidified serum test and the test for the Donath-Landsteiner antibody were carried out as described Electrophoresis of glucose 6-phosphate dehydrogenase. Blood was collected in one fifth volume of ACD solution and the red cells washed twice by centrifugation in normal saline (containing 0.1 mM. EDTA). The sedimented cells were hemolyzed in 10 M. NADP and the hemolysates subjected to starch gel electrophoresis as previously described.8 1968, with a complaint of " passing dark urine, like blood, " which had From the Subdepartment of Hematology,