THALASSEMIA results from an imbalance in the synthesis of a- and ß-globin Chains. To date we know of > 1000 naturally occurring inherited mutations that affect either the structure or synthesis of the a- and ß-like globin chains.  Thalassemia occurs when there is a deficiency in a globin expression and ß thalassemia occurs when ß globin synthesis is downregulated. Many different mutant alleles have been selected to reach very high frequencies in tropical and subtropical regions of the world because heterozygotes are, to some extent, protected from the effects of falciparum malaria. Carriers of a and ß thalassemia are clinically normal but the associated hypochromic microcytic blood picture requires careful diagnostic screening to differentiate it from other conditions with similar hematological pictures (e.g., iron deficiency and sideroblastic anemia). In areas where a and ß thalassemia commonly occur, compound heterozygotes and homozygotes for these mutations may suffer from the clinically severe forms of  thalassemia (HbH disease and Hb Bart’s hydrops fetalis) and ß thalassemia (ß thalassemia major and the less severe ß thalassemia intermedia). A summary of the key clinical syndromes (a) and pathophysiology of a (b) and ß (c) thalassemia. The consequences of reduced a and ß globin synthesis are indicated by dotted lines. Note, a thalassemia affects both the fetus and adult whereas ß thalassemia only becomes apparent after birth. HbF may persist or become re-activated during adult hematopoiesis in ß thalassemia.

Epidemiology : thalassemia is the world’s most common monogenic disorder. In areas where thalassemia is prevalent, the carrier frequency of  thalassemia varies from 1% (e.g., in Southern Spain) to 90% (e.g., the tribal populations of India). Similarly, the carrier frequency of ß thalassemia may vary from 1% (e.g., in Northern Italy) to 50–70% (e.g., ß-E in some regions of southeast Asia). Considerable variation occurs even within a single country. It has been estimated that worldwide there are 270 million carriers of mutant globin alleles which can potentially cause severe forms of thalassemia and hemoglobinopathy (including sickle cell disease), and every year some 300–400,000 severely affected infants are bornref. > 95% of these affected births occur in Asia, India and the Middle East. However, over the past few decades there has been considerable mobility in the world’s populations so that now in Australasia, Europe and North America a significant proportion of recent immigrants originate from countries in which thalassemia commonly occurs. Therefore, the management of families from ethnic minorities, at risk of producing offspring with severe life-threatening forms of thalassemia, has become a new important aspect of hematologic practice. It has also been noted over the past 50 years that, as the world economy improves and the overall infant mortality rate falls, thalassemia is rapidly emerging as a major economic and health burden in developing countries since infants with thalassemia who would otherwise have died from infection and malnutrition now survive and require lifelong treatment. Therefore, worldwide, thalassemia is an enormous and ever-increasing hematologic problem in both developed and developing countriesref. Today’s epidemiology of thalassemia is strikingly different from that of the past. Thalassemia is now a heterogeneous group of diseases with varied ethnicities, phenotypes and treatments. In the past, Hb E-ß-thalassemia and Hb H disease were rarely seen in North America and Europe. Now, as a result of changing demographics, these disorders have become more common than classical ß-thalassemia major in many regionsref1, ref2, ref3, ref4, ref5. HbH, HbH-Constant Spring and homozygous a-thalassemia affect at least a million people worldwideref. The natural history of these disorders is highly variable and poorly studied. The phenotype, for patients with similar mutations, can range from asymptomatic to transfusions dependency. Ethnic groups originating from regions with malaria have a high frequency of thalassemia mutations. There are almost 300 million carriers of hemoglobin disorders in the world, with the majority living in South East Asiaref1, ref2, ref3, ref4. Worldwide, the Asian, Indian and Middle Eastern regions account for 95% of thalassemia births. The frequency of a-thalassemia reaches 25% in Thailand, and HbE approaches 60% in many regions of Thailand, Laos and Cambodia. Hb Constant Spring is found in 1–10% of the population in these areas. The WHO estimates that Thailand will have over 250,000 symptomatic thalassemia patients diagnosed over the next few decadesref1, ref2, ref3, ref4, ref5. At least 100,000 new cases of HbE-ß-thalassemia are expected. Similar estimates are predicted for India, Sri Lanka and Malaysiaref. In southern China, with a population of over 350 million, approximately 5% are carriers for a-thalassemia and 4% for ß-thalassemia or HbEref. In the last decade, 75% of immigrants to North America came from areas where thalassemia mutations were prevalent. These demographic changes have resulted in thalassemia becoming a more significant health problem in North America. Hb E-ß-thalassemia and a-thalassemia disorders are now the most common thalassemias in California. In response to the high prevalence of -thalassemia and its associated morbidity, California has initiated universal newborn screening for HbH and HbH-Constant Springref. Characterizing the molecular defects underlying  and ß thalassemia has transformed the management of these conditions in many developed countries. Over the past 25 years, throughout Europe, Australasia and North America comprehensive control programs involving education, counselling and pre-natal diagnosis have succeeded in limiting the numbers of new births of affected individuals. One of the best-documented examples of this approach has been in Cyprus where thalassemia was first recognized in the 1940s following the eradication of malaria. With a population size of ~700,000 and a carrier frequency for ß thalassemia of 15–17%, in the early 1970s it was estimated that to treat all severely affected children would require 78,000 units of blood per year, 40% of the population would be donors and the total cost to the health service would exceed the island’s health budgetref. With judicious application of a control program there are now fewer than 600 severely affected patients with thalassemia in Cyprus and only 2-3 new cases arising each year. A similar highly effective control program was also established by pioneering work in Sardiniaref. In First World countries the outlook for the relatively small numbers of patients with ß thalassemia major and intermedia has also dramatically improved over the last 25 years.
Pathogenesis : uneffective erythropoiesis : decreased or no synthesis of one or more kinds of globin => precipitation of the remaining kinds => peripheral hemolysis / hemocatheresis. Complicated by parvovirus B19 infection Laboratory examinations :
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