Hydrops Fetalis Caused by a-Thalassemia: An Emerging Health Care Problem

HYDROPS FETALIS is a serious disorder, usually indicative of an ominous prognosis for the affected fetus. There are many causes, including both hereditary and acquired diseases.1-3 In southeast Asia, a-thalassemia is the most common cause of fetal hydrops, accounting for 60% to 90% of the cases.4-7 With population migrations during the past decades, this syndrome is now seen in increasing numbers in other parts of the world. a-Thalassemia is caused by mutations of the a-globin genes, leading to decreased or absent a-globin chain production from the affected genes. a-Globin chains are the subunits for both fetal hemoglobin (a2g2) and adult hemoglobin (a2b2). Therefore, severe a-thalassemias can cause anemia in fetuses and in adults. Together with b-thalassemias which are caused by mutations of the b-globin genes, the thalassemias are among the most common single gene mutations in humans.8 They are found mostly in areas where malaria was and may still be endemic. Each person normally has a total of four a-globin genes, two of which are encoded in tandem (in cis) on each chromosome 16 (Fig 1). There are a-thalassemia deletions that remove either one or two a-globin genes on each chromosome 16.9-11,11a If both parents are carriers of a deletion removing two a-globin genes in cis on one chromosome 16, there is a one in four risk that in each pregnancy, the fetus might inherit both parental deletional mutations, and lack all a-globin genes. Because a-globin chains normally are produced throughout gestation, fetuses without a-globin genes would suffer from severe anemia, and thus hypoxia, heart failure, and hydrops fetalis. They would usually survive in utero until the third trimester of gestation when they would succumb to their genetic defects. In contrast to a normal fetus whose major hemoglobin is Hb F (a2g2), these fetuses have primarily Hb Bart’s (g4). This disorder, first described in 1960, is known as homozygous a-thalassemia or Hb Bart’s hydrops fetalis syndrome.12,13