Introduction

The thalassemias are a diverse group of genetic blood diseases characterized by absent or decreased production of normal hemoglobin, resulting in a microcytic anemia of varying degree. The thalassemias have a distribution concomitant with areas where P. falciparum malaria is common. The alpha thalassemias are concentrated in Southeast Asia, Malaysia, and southern China. The beta thalassemias are seen primarily in the areas surrounding Mediterranean Sea, Africa and Southeast Asia. Due to global migration patterns, there has been an increase in the incidence of thalassemia in North America in the last ten years, primarily due to immigration from Southeast Asia.

In the normal adult, hemoglobin A, which is composed of two alpha and two beta globins (a²b²), is the most prevalent, comprising about 95% of all hemoglobin. Two minor hemoglobins also occur: hemoglobin A₂, composed of two alpha and two delta globins (a²d²) comprises 2-3.5% of hemoglobin, while hemoglobin F, composed of two alpha and two gamma globins (a²g²), comprises less than 2% of hemoglobin.

Hemoglobin F, or fetal hemoglobin, is produced by the fetus in utereo and until about 48 weeks after birth. Hgb F has a high oxygen-affinity in order to attract oxygen from maternal blood and deliver it to the fetus. After birth, the production of adult hemoglobin rapidly increases and fetal hemoglobin production drops off.

The genes controlling globin production are on chromosome 16 (alpha a globin genes) and chromosome 11 (beta b, gamma g, and delta d genes). As seen in the diagram, the alpha globin molecule concentration is rather stable in fetal and adult life, because it is needed for both fetal and adult hemoglobin production. The beta globin appears early in fetal life at low levels and begins to rapidly increase after 30 weeks gestational age, reaching a maximum about 30 weeks postnatally. The gamma globin molecule reaches a high level early in fetal life at about 6 weeks and begins to decline about 30 weeks gestational age, reaching a low level about 48 weeks postgestational age. The delta globin appears at a low level at about 30 weeks gestational age and maintains a low profile throughout life.

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