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Fetal hemoglobin (hemoglobin F) in health and disease

Martin H Steinberg, MD
Swee Lay Thein, MD, FRCP, FRCPath, DSc
Section Editor
William C Mentzer, MD
Deputy Editor
Jennifer S Tirnauer, MD


Fetal hemoglobin (hemoglobin F, HbF) is the major hemoglobin present during gestation; it constitutes approximately 60 to 80 percent of total hemoglobin in the full-term newborn. It is almost completely replaced by adult hemoglobin (hemoglobin A, HbA) by approximately 6 to 12 months of age, and it amounts to less than 1 percent of total hemoglobin in the adult.

As a minor hemoglobin in the normal child and adult, HbF has little in the way of clinical relevance in normal physiology. However, it is assuming ever greater importance in certain of the hemoglobinopathies, in which congenital, acquired, and drug-induced increases in HbF have been shown to improve the clinical performance of affected individuals with sickle cell disease and beta thalassemia. This important subject is discussed in depth separately. (See "Hydroxyurea use in sickle cell disease".)

The biology of HbF in health and disease will be discussed here. Reviews of the other normal hemoglobins (eg, hemoglobin A, hemoglobin A2) and the most common hemoglobin mutations are presented separately. (See "Structure and function of normal hemoglobins" and "Introduction to hemoglobin mutations".)


Evolution — Hemoglobin evolved from ancient hemoproteins by gene duplication, gene conversion (non-reciprocal exchange of genetic material between two linked homologous genes), translocation to different chromosomes, and mutations that caused changes in the primary structure and properties of globin and their various genetic regulatory regions [1].

Human alpha- (HBA1 and HBA2) and beta- (HBB) globin gene clusters diverged from their predecessors approximately 450 million years ago, with modern adult hemoglobin becoming a heterotetramer of the products of these two genes (alpha2beta2).


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