Hereditary persistence of fetal hemoglobin (HPFH)

Fetal hemoglobin F (HbF) as a percentage of total hemoglobin is low (<0.5%) to undetectable in adults. In some ethnic groups, especially where other hemoglobinopathies are also more prevalent, elevated HbF persists beyond the first few months of life in 10-15% of the population due to genetic factors. Affected individuals show no clinical symptoms and an unremarkable blood count. This condition is called hereditary persistence of fetal hemoglobin (HPFH).

Hereditary persistence of fetal hemoglobin is caused by deletions and non-deletional mutations in the β-globin gene complex or other regulatory regions. The most common cause is large deletions affecting both the δ- and β-globingen. Mechanistically, it could be shown that the β-globin gene competes with the γ-globin genes for the superordinate control unit of the β-globin gene complex (locus control region, LCR). If the promoter region of the β-globin gene fails, this results in increased expression of the γ-globin genes and thus increased production of HbF.

In contrast to HPFH, the γ-globin genes are not activated to the same extent in δβ-thalassemia, which is also based on deletions of the two globin genes, and therefore cannot compensate for the loss of the deleted β-globin allele. In hereditary persistence of fetal hemoglobin, typically 15-30% HbF and balanced production of α- and non-α-globin chains are found, whereas in δβ-thalassemia only 5-15% HbF and an imbalance between globin chains is found. Despite these differences, HPFH and δβ-thalassemia are now considered less as two entities and more as a continuum with a smooth transition.