Rapid destruction of newly synthesized excess beta-globin chains in HbH disease

A subject with HbG Philadelphia-HbH disease exhibited an unusually high alpha/beta synthesis ratio; when peripheral blood was tested in vitro on several occasions, ratios of 0.63 - 0.89 were obtained after incubations of 30-120 min. HbH amounted to 5%-8% of the circulating hemoglobin. Rapid destruction of excess newly synthesized beta-globin was demonstrated in kinetic and pulse-chase experiments. After 2 min of incubation, the alpha/beta synthesis ratio was 0.48; this figure rose to 0.89 by 30 min. The zero time alpha/beta ratio was estimated to be 0.35. The degradation of beta-chains was calculated to proceed at approximately one-half the rate of beta-globin synthesis; this result was confirmed by the loss of 50% of the specific activity in beta-chains during 9 min of a chase experiment following a 10-min radioactive pulse. The results suggest that efficient proteolysis may be responsible, in some blacks, for the low levels of excess beta-globin chains in HbH disease as well as for the mildness of the clinical disorder.