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754 Part VI: The Erythrocyte Chapter 48: The Thalassemias: Disorders of Globin Synthesis 755

the children still are at school and warning carriers about the potential countries of the world. In many developing countries in which there is
risks of marriage to another carrier. Few data are available about the a very high frequency of thalassemia, there are very limited facilities for
value of programs of this type; a pilot study in Greece was unsuccess- their diagnosis and management. Because many of these countries are
ful. Because it is believed this approach will not be successful in many going through the epidemiologic transition, which involves improve-
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populations, considerable effort has been directed toward developing ments in nutrition, cleaner water supplies, and better public health ser-
prenatal diagnosis programs. vices, babies with serious forms of thalassemia who previously would
Prenatal diagnosis for prevention of thalassemia entails screen- have died of infection or profound anemia are now surviving to present
ing mothers at the first prenatal visit, screening the father in cases in for treatment.
which the mother is a thalassemia carrier, and offering the couple the Approaches to the better control and management of the thalas-
possibility of prenatal diagnosis and termination of pregnancy if both semias in developing countries have been reviewed. 303,304 They include
mother and father are carriers of a gene for a severe form of thalassemia. the development of partnerships between centers in the developed and
Currently, these programs are devoted mainly to prenatal diagnosis of developing countries for training workers in this field, and, once these
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the severe transfusion-dependent forms of homozygous β or β -thalas- partnerships are developed, for the further evolution of partnerships
semia. Considerable experience has also been gained in prenatal diag- between those developing countries where there is knowledge and
nosis of mothers at risk for having a fetus with the hemoglobin Bart expertise of the field with those where no knowledge or facilities exist.
hydrops syndrome, considering the distress caused by a long and diffi- Without organizations along these lines, the thalassemias will con-
cult pregnancy and the obstetric problems resulting from the birth of a tinue to cause the premature death of hundreds of thousands of infants
hydropic infant with a massive placenta. worldwide.
The first efforts at prenatal detection of β-thalassemia used fetal
blood sampling and globin-chain synthesis analysis carried out at REFERENCES
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contamination of fetal DNA and nonpaternity. 16. Siniscalco M, Bernini L, Filippi G, et al: Population genetics of haemoglobin variants,
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the Mediterranean region and the Middle East, and in parts of the natural selection by malaria. Nature 321:744, 1986.
Indian subcontinent and Southeast Asia. Several approaches continue 18. Allen SJ, O’Donnell A, Alexander NDE, et al: α -Thalassemia protects children against
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disease due to malaria and other infections. Proc Natl Acad Sci U S A 94:14836, 1997.
to be explored in an attempt to avoid the use of invasive procedures 19. Williams TN: Red blood cell defects and malaria. Mol Biochem Parasitol 149:121, 2006.
like chorion villous sampling. A variety of methods are being used to 20. Williams TN, Mwangi TW, Wambua S, et al: Negative epistasis between the malar-
harvest fetal DNA from fetal cells in maternal blood or from maternal ia-protective effects of alpha -thalassemia and the sickle cell trait. Nat Genet 37:1253,
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tation diagnosis of thalassemias. 300,301 There is every expectation that 21. Williams TN, Maitland K, Bennett S, et al: High incidence of malaria in α-thalassemic
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some of these approaches will reach the clinic in the near future. 302 22. Cockburn IA, Mackinnon MJ, O’Donnell A, et al: A human complement receptor 1
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THALASSEMIA AS A GLOBAL HEALTH 23. Weatherall DJ: Genetic variation and susceptibility to infection: The red cell and
malaria. Br J Haematol 141:276, 2008.
PROBLEM 24. Williams TN, Weatherall DJ: World distribution, population genetics, and health bur-
The remarkable advances in the diagnosis, prevention, and treatment of den of the hemoglobinopathies. Cold Spring Harb Perspect Med 2:a011692, 2012.
the thalassemias described in this chapter are only relevant to the richer 25. Orkin SH: The duplicated human α globin genes lie close together in cellular DNA. Proc
Natl Acad Sci U S A 75:5950, 1978.

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