The Prevention of Thalassemia

Abstract

The thalassemias are among the most common inherited diseases worldwide, affecting individuals originating from the Mediterranean area, Middle East, Transcaucasia, Central Asia, Indian subcontinent, and Southeast Asia. As the diseases require long-term care, prevention of the homozygous state constitutes a major armament in the management. This article discusses the major prevention programs that are set up in many countries in Europe, Asia, and Australia, often drawing from the experience in Sardinia. These comprehensive programs involve carrier detections, molecular diagnostics, genetic counseling, and prenatal diagnosis. Variability of clinical severity can be attributable to interactions with a-thalassemia and mutations that increase fetal productions. Special methods taht are currently quite expensive and not widely applicable are preimplantation and preconception diagnosis. The recent successful studies of fetal DNA in maternal plasma may allow future prenatal diagnosis that is noninvasive for the fetus.

Thalassemia 2016: Modern medicine battles an ancient disease

“…Although efforts at perfecting the technique are underway, preimplantation genetic diagnosis is not perfect. Using this technique, the rate of successful pregnancy is at best around 30% [16], which is considerably lower than the rate of spontaneous conception in a fertile couple who would not normally need reproductive intervention other than for embryo selection. Furthermore, it is challenging to employ this technique for b-thalassemia which is usually due to point mutations [17].…”

Hemoglobin Variants: Biochemical Properties and Clinical Correlates

“…Thus, an amino acid substitution that reduces O 2 affinity exacerbates the effects of a sickling mutation in the same globin chain. Several other Hb variants modulate the severity of sickle cell anemia (see also Cao and Kan 2012;Schechter and Elion 2012;Serjeant and Rodgers 2012). For example, g globin inhibits polymerization of HbS (Nagel et al 1979).…”

“…The most common and medically important Hb variants include HbS (Cao and Kan 2012;Lettre 2012;Schechter and Elion 2012;Serjeant and Rodgers 2012;Williams and Weatherall 2012), HbC (Cao and Kan 2012;Lettre 2012;Schechter and Elion 2012;Serjeant and Rodgers 2012;Williams and Weatherall 2012), HbE (see the sections on Selected Variants that Illustrate Important Aspects of Hemoglobin Biology and Variants that Affect Multiple Hemoglobin Functions; see also Musallam et al 2012), and some thalassemias (e.g., "thalassemic hemoglobinopathies"), all of which are under positive genetic selection because they confer survival advantages in areas where malaria is endemic (Weatherall and Clegg 2001). In addition to these prevalent mutant proteins, there are also .1000 other known naturally occurring Hb variants, which are rare individually but common collectively.…”

Management of the Thalassemias

“…Unless this precaution is taken, babies with various forms of thalassemia of intermediate severity may be placed on lifelong unnecessary transfusion. The important features to observe before long-term transfusion is considered include the patterns of growth and growth velocity, activity compared with infants of the same age, the occurrence of progressive splenomegaly, and early evidence of any skeletal 3 See Cao and Kan (2013). deformity.…”