here are two major phenotypes. he deletion of all four a-globin chain genes (--/--) characterizes homozygous a-thalassemia. Because a-chains are contained in fetal hemoglobin, the fetus is afected. When none of the four genes
TABLE 56-4. Genotypes and Phenotypes of .-Thalassemia Syndromes
Normal ../.. Normal .+-Thalassemia heterozygote -'/.. } Normal; silent carrier ../-. .+-Thalassemia homozygotea -./-. } a-Thalassemia minor-mild .°-Thalassemia heterozygoteb --/.. hypochromic microcytic anemia Compound heterozygous .0/.+ --/-. Hgb H (34) with moderate-to severe hemolytic anemia Homozygous .-thalassemia --/--Hgb Bart ('4) disease, hydrops fetalis
African Americans. bMore common in Asian Americans.
are expressed, no a-globin chains are produced, and instead hemoglobin Bart (14) and hemoglobin H (34) are formed as abnormal tetramers that cannot transport oxygen (Chap. 7, p. 131).
he relative frequency of a-thalassemia minor, hemoglobin H disease, and hemoglobin Bart disease varies remarkably among racial groups. All of these variants are encountered in Asians.
In those of African descent, although a-thalassemia minor has a frequency approximating 2 percent, hemoglobin H disease is rare and hemoglobin Bart disease is unreported. This is because
Asians usually have .0-thalassemia minor inherited with both gene deletions typically from the same chromosome (--/..), whereas blacks usually have .+-thalassemia minor in which one gene is deleted from each chromosome (-xl-x).
Diagnosis of 3-thalassemia minor and a-thalassemia major in the fetus can be accomplished by DNA analysis using molec ular techniques (Piel, 2014). Fetal diagnosis of hemoglobin yakul, 2009; Srivorakun, 2009). Molecular genetic testing for
HBAl and HBA2 identifies 90 percent of deletions and 10 percent of point mutations in afected individuals (Galanello, 2011 b).
Important obstetrical aspects of some a-thalassemia syndromes depend on the number of gene deletions in a given woman. he silent carrier state with one gene deletion is of no consequence. Deletion of two genes resulting in a-thalassemia minor is characterized by minimal-to-moderate hypochromic micro cytic anemia. This is due to either .r_ or .+-thalassemia trait, and thus genotypes may be -xla or --la.. Diferentiation is possible only by DNA analysis (Piel, 2014). Because no other clinical abnormalities accompany either form of a-thalassemia minor, it often goes unrecognized and is usually of no maternal consequence (Hanprasertpong, 2013). The fetus with these forms of thalassemia minor will have hemoglobin Bart at birth, but as its levels drop, it is not replaced by hemoglobin H. Red cells are hypochromic and microcytic, and the hemoglobin concentration is normal to slightly depressed.
Hemoglobin H disease (34) results from the compound heterozygous state for .0_ plus .+-thalassemia with deletion of three of four alpha genes (--I-x). With only one functional a-globin gene per diploid genome, the newborn will have abnormal red cells containing a mixture of hemoglobin Bart (14), hemoglobin H (34)' and hemoglobin A. The neonate appears normal but soon develops hemolytic anemia as most of the hemoglobin Bart is replaced by hemoglobin H. In adults, anemia is moderate to severe and usually worsens during pregnancy.