Favism is an acute
hemolytic anemia triggered by ingestion of fava beans in genetically susceptible subjects with severe
deficiency of glucose-6-phosphate dehydrogenase (G6PD) activity. Erythrocytes from 10 favic patients had constantly and markedly increased
calcium levels, as compared with values detected in 4 asymptomatic G6PD-deficient controls. Correspondingly, the
calcium permeability of erythrocytes, estimated as the fraction of intracellular
calcium exchangeable with externally added 45Ca2+, was invariably enhanced in
favism and returned to normal patterns after several months from the acute hemolytic crisis. In favic patients, the levels of erythrocyte
calcium ATPase activities showed wide variability, ranging from 2.0-12.9 mumol Pi/ml RBC/h, while control values in asymptomatic G6PD-deficient subjects were 10.62 +/- 2.03 mumol Pi/ml RBC/h. Analysis of the
calcium ATPase in situ in erythrocyte membranes from favic patients showed the same molecular mass of 134 kD as observed in the control subjects. Exposure of G6PD-deficient erythrocytes in vitro to autoxidizing
divicine, a
pyrimidine aglycone strongly implicated in the pathogenesis of
favism which leads to late accumulation of intracellular
calcium, caused: (i) a marked inactivation of
calcium ATPase, without changes in the molecular mass of 134 kD; and (ii) the concomitant loss of
spectrin, band 3 and band 4.1, all known substrates of the
calcium activated
procalpain-
calpain proteolytic system. Thus, the increased intraerythrocytic
calcium apparently results in the degradation of
calcium ATPase observed in some favic patients. It is proposed that both enhanced
calcium permeability and a
calcium-stimulated degradation of the
calcium pump are the mechanisms responsible for the perturbation of erythrocyte
calcium homeostasis in
favism.