Prediction of severity of disease in homozygous β thalassemia (β thal)

Abstract

The clinical consequences of homozygous β thal are variable. We have studied globin chain synthesis in the peripheral blood reticulocytes of the parents of patients with homozygous β thal to determine the likelihood of mild and sever β thal in families in which both parents have thal trait. Peripheral blood was incubated with U 14C leucine. The ratio of the specific activities of β and α chain separated by urea CMC chromatography (β/α ratio) was determined. The β/α ratios of 14 parents of patients with severe disease was compared to those of 10 parents of patients with mild disease. The mean β/α ratio in the former group of parents was 0.49 with a narrow standatrd deviation of 0.06. The mean ratio in the group of parents of patients with mild disease was 0.68 with a wider standard deviation of 0.21. Two patterns were observed in the milder group: (1) the ratio in one parent was close to 0.50, while the other parent had a significantly higher ratio (0.71 to 1.09), and (2) both parents had moderately elevated ratios (0.65). The higher ratios in the milder group may represent a milder β thal gene or the co-inheritance of an α thal gene, either one of which reduces the severity of homozygous β thal. We conclude that the study of peripheral blood globin chain synthesis in prospective parents with β thal trait may be extremely useful for estimating the potential severity of homozygous β thal in their offspring.