These syndromes are the most common single-gene disorders worldwide, and up to 200 million people carry a gene for one of these hemoglobinopathies (Chap. 56, p. 1084). Some individuals with thalassemia have microcytic anemia secondary to decreased synthesis of either a-or 3-hemoglobin chains. In general, deletions of a-globin chains cause a-thalassemia, whereas mutations in 3-globin chains cause 3-thalassemia. Less commonly, an a-globin chain mutation also causes a-thalassemia.
The number of a-globin genes that are deleted may range from one to all four. If two a-globin genes are deleted, both may be deleted from the same chromosome-cis coniguration (aal--), or one may be deleted from each chromosometrans configuration (a-/a-). Alpha-thalassemia trait is common among individuals of African, Mediterranean, Middle Eastern, West Indian, and Southeast Asian descent and results in mild anemia. he cis coniguration is more prevalent among Southeast Asians, whereas those of African descent are more likely to inherit the trans configuration. Clinically, when both parents carry cis deletions, ofspring are at risk for an absence of a-hemoglobin, called Hb Barts disease. This typically leads to hydrops and fetal loss as discussed in Chapter 15 (p. 309).
Detection of a-thalassemia or a-thalassemia trait is based on molecular genetic testing and is not detectable using hemoglobin electrophoresis. Because of this, routine carrier screening is not ofered. If there is microcytic anemia in the absence of iron deiciency and the hemoglobin electrophoresis is normal, then testing for a-thalassemia can be considered, particularly among individuals of Southeast Asian descent (American College of Obstetricians and Gynecologists, 2015).
Mutations in 3-globin genes may cause reduced or absent production of 3-globin chains. If the mutation afects one gene, it results in 3-thalassemia minor. If both copies are afected, the result is either 3-thalassemia major-termed Cooley anemiaor 3-thalassemia intermedia. Because of reduced production of hemoglobin A among carriers, electrophoresis demonstrates elevated levels of hemoglobins that do not contain 3-chains. hese include hemoglobins F and A2.
3-Thalassemia minor is more common among individuals of African, Mediterranean, and Southeast Asian descent. The American College of Obstetricians and Gynecologists (2015) recommends that they be ofered carrier screening with hemoglobin electrophoresis, parti�ularly if found to have microcytic anemia in the absence of iron deiciency. Hemoglobin A2 levels exceeding 3.5 percent conirm the diagnosis. Other ethnicities at increased risk include those of Middle Eastern, West Indian, and Hispanic descent .