Heterocellular hereditary persistence of fetal haemoglobin (heterocellular HPFH) and its interaction with beta thalassaemia.

Abstract

Summary. Three families have been observed in which a gene for heterocellular hereditary persistence of fetal haemoglobin (HPFH), probably identical to that previously described as Swiss type HPFH, has been inherited together with β thalassaemia. The interaction of these two genes results in β thalassaemia heterozygotes with unusually high levels of fetal haemoglobin, 6–15%, heterogeneously distributed. In four individuals with Hb S‐β thalassaemia who also inherited a heterocellular HPFH gene, Hb F levels of up to 25% were observed, resulting in an extremely mild clinical condition. Globin synthesis studies show less chain imbalance in the heterocellular HPFH‐β thalassaemia compound heterozygotes than in the heterozygous β thalassaemia members of these families. Age stratification of the red cells by centrifugation showed enrichment of Hb F and Hb F‐containing cells (F‐cells) in the older cell population. It is suggested that the effect of the heterocellular HPFH gene is to increase the size of the F‐cell population and that preferential survival of that expanded F cell population leads to the high levels of Hb F which result when heterocellular HPFH interacts with β thalassaemia or Hb S. The mild clinical condition which results from such interaction may explain part of the heterogeneity of the β thalassaemia syndromes and suggests that the induction of even relatively small increases in the production of Hb F in these conditions could be of potential therapeutic benefit.