Although uncommon in the United States, hemoglobin E is the second most frequent hemoglobin variant worldwide. The heterozygous E trait is common in Southeast Asia. Hurst and coworkers (1983) identified homozygous hemoglobin E, hemoglobin E plus 3-thalassemia, or hemoglobin E trait in 36 percent of Cambodians and 25 percent of Laotians. Hemoglobin EE is associated with little or no anemia, hypochromia, marked microcytosis, or erythrocyte targeting. Kemthong and colleagues (2016) studied 1073 women and 2146 controls and found that hemoglobin E trait does not increase pregnancy risks other than asymptomatic bacteriuria. Conversely, doubly heterozygous E-3-thalassemia is a common cause of severe childhood anemia in Southeast Asia (DeLoughery, 2014). In a cohort study of 54 women with singleton pregnancies, Luewan and associates (2009) reported a threefold greater risk of preterm birth and fetal-growth restriction in afected women. It is unclear if hemoglobin SE disease is ominous during pregnancy.
• Hemoglobinopathy in the Newborn
Neonates with homozygous SS, SC, and CC disease can be identiied accurately at birth by cord blood electrophoresis. The United States Preventive Services Task Force recommends that all newborns be tested for sickle-cell disease (Lin, 2007). In most states, such screening is mandated by law and performed routinely (Chap. 32, p. 614).
Many tests are available to detect sickle-cell disease ante natally. Most are DNA based and use chorionic villus samples or amnionic fluid specimens (American College of Obstetricians and Gynecologists, 2015). Several mutations that encode hemoglobin S and other abnormal hemoglobins can be detected by targeted mutation analysis and polymerase chain reaction-based techniques (Chap. 13, p. 270).
Hundreds of mutations afect genes that control hemoglobin production. Some of these impair synthesis of one or more of the normal globin peptide chains and may result in a clinical syndrome characterized by varying degrees of inefective erythropoiesis, hemolysis, and anemia (Benz, 2015). Thalassemias are classiied according to the globin chain that is deficient. The two major forms involve impaired production or instability of a-peptide chains to cause a-thalassemia or of 3-chains to cause 3-thalassemia. hese may form from point mutations, deletions, or translocations involving the .-or non-a-globin gene (Leung, 2012).
Because there are four a-globin genes, the inheritance of a-thalassemia is more complicated than for 3-thalassemia (Piel, 2014). Possible genotypes and phenotypes are shown in
Table 56-4. Clinical severity closely correlates with the degree of a-globin chains synthesis impairment. In most populations, the a-globin chain "cluster" or gene loci are doubled on chromosome 16. Similarly, ther, chains are duplicated. Thus, the normal genotype for diploid cells can be expressed as ../.. and "r /,,. here are two main groups of a-thalassemia determinants: .0-thalassemia is the deletion of both loci from one chromosome (--/..), whereas .+ -thalassemia is the loss of a single locus from one allele (-./.. heterozygote) or a loss from each allele (-./-.homozygote).