Thalassemia
Updates to Article Attributes
Thalassaemia is an autosomal recessivehaemoglobinopathy that originated in the Mediterranean region. The genetic defect causes a reduction in the rate of globin chain synthesis which causes the formation of abnormal haemoglobin molecules. The resultant microcytic anaemia is the characteristic presenting symptom of the thalassaemias.microcytic anaemia that
Thalassemia is a quantitative problem of globin synthesis, whereas sickle-cell disease (a is a qualitative problem of synthesis of an incorrectly functioning globin.haemoglobinopathy)
Pathophysiology
Normal adult haemoglobin is composed of HbA (98%) and HbA2 (2%). HbA contains two α globin chains / two β globin chains, and HbA2 contains two α globin chains / two δglobin chains. They are arranged into a heterotetramer. Thalassaemia patients produce a deficiency of either α or β globin, unlike sickle-cell disease, which produces a specific mutant form of β globin.
The thalassemias are classified according to which chain of the haemoglobin molecule is affected. In α thalassemias, production of the α globin chain is reduced, while in β thalassemia production of the β globin chain is reduced.
The β globin chains are encoded by a single gene on chromosome 11; α globin chains are encoded by two closely linked genes on chromosome 16. Thus, in a normal person with two copies of each chromosome, there are two loci encoding the β chain, and four loci encoding the α chain. Deletion of one of the α loci has a high prevalence in people of African or Asian descent, making them more likely to develop α thalassemias. β thalassemias are common in Africans, but also in Greeks and Italians.
The thalassaemia trait may confer a degree of protection against malaria, which confers a selective survival advantage on carriers.
Radiographic features
Skeletal
Marrow proliferation consists of expansion of the medulla, thinning of cortical bone, and resorption of cancellous bone resulting in a generalized loss of bone density.
- skull: classic "hair-on-end" appearance
- facial bones: rodent facies
- ribs: "rib-within-a-rib" appearance, noted particularly in the middle and anterior portions of the ribs
- extramedullary haematopoiesis
- premature fusion of the epiphyses
- osteoporosis 4
Gastrointestinal: hepatobilliary
History and etymology
Named for the the Greek word for "sea" (θάλασσα - thálassa), Cooley and Lee described bone abnormalities and severe anemia with associated splenomegaly in 1921 5.
-<p><strong>Thalassaemia</strong> is an <a href="/articles/autosomal-recessive">autosomal recessive</a> <a href="/articles/microcytic-anaemia">microcytic anaemia</a> that originated in the Mediterranean region. The genetic defect causes a reduction in the rate of <a href="/articles/globin-chain">globin chain</a> synthesis which causes the formation of abnormal <a href="/articles/haemoglobin">haemoglobin </a>molecules. The resultant anaemia is the characteristic presenting symptom of the thalassaemias.</p><p>Thalassemia is a quantitative problem of globin synthesis, whereas <a href="/articles/sickle-cell-disease">sickle-cell disease</a> (a <a href="/articles/haemoglobinopathy">haemoglobinopathy</a>) is a qualitative problem of synthesis of an incorrectly functioning globin.</p><h4>Pathophysiology</h4><p>Normal adult haemoglobin is composed of HbA (98%) and HbA<sub>2</sub> (2%). HbA contains two <a href="/articles/a-globin-chains">α globin chains</a> / two <a href="/articles/b-globin-chains">β globin chains</a>, and HbA<sub>2</sub> contains two <a href="/articles/a-globin-chains">α globin chains</a> / two <a href="/articles/globin-chains">δ</a><a href="/articles/a-globin-chains"> </a><a href="/articles/globin-chains">globin chains</a>. They are arranged into a heterotetramer. Thalassaemia patients produce a deficiency of either α or β globin, unlike sickle-cell disease, which produces a specific mutant form of β globin.</p><p>The thalassemias are classified according to which chain of the haemoglobin molecule is affected. In α thalassemias, production of the α globin chain is reduced, while in β thalassemia production of the β globin chain is reduced.</p><p>The β globin chains are encoded by a single gene on chromosome 11; α globin chains are encoded by two closely linked genes on chromosome 16. Thus, in a normal person with two copies of each chromosome, there are two loci encoding the β chain, and four loci encoding the α chain. Deletion of one of the α loci has a high prevalence in people of African or Asian descent, making them more likely to develop α thalassemias. β thalassemias are common in Africans, but also in Greeks and Italians.</p><p>The <a href="/articles/thalassemia-trait">thalassaemia trait</a> may confer a degree of protection against malaria, which confers a selective survival advantage on carriers.</p><h4>Radiographic features</h4><h5>Skeletal</h5><p>Marrow proliferation consists of expansion of the medulla, thinning of <a href="/articles/cortical-bone">cortical bone</a>, and resorption of <a href="/articles/cancellous-bone">cancellous bone</a> resulting in a generalized loss of bone density.</p><ul>-<li>skull: classic "<a href="/articles/hair-on-end-sign">hair-on-end</a>" appearance</li>- +<p><strong>Thalassaemia</strong> is an autosomal recessive <a href="/articles/haemoglobinopathy">haemoglobinopathy</a> that originated in the Mediterranean region. The genetic defect causes a reduction in the rate of <a href="/articles/globin-chain">globin chain</a> synthesis which causes the formation of abnormal <a href="/articles/haemoglobin">haemoglobin </a>molecules. The resultant <a href="/articles/microcytic-anaemia">microcytic anaemia</a> is the characteristic presenting symptom of the thalassaemias.</p><p>Thalassemia is a quantitative problem of globin synthesis, whereas <a href="/articles/sickle-cell-disease">sickle-cell disease</a> is a qualitative problem of synthesis of an incorrectly functioning globin.</p><h4>Pathophysiology</h4><p>Normal adult haemoglobin is composed of HbA (98%) and HbA<sub>2</sub> (2%). HbA contains two <a href="/articles/a-globin-chains">α globin chains</a> / two <a href="/articles/b-globin-chains">β globin chains</a>, and HbA<sub>2</sub> contains two <a href="/articles/a-globin-chains">α globin chains</a> / two <a href="/articles/globin-chains">δ</a><a href="/articles/a-globin-chains"> </a><a href="/articles/globin-chains">globin chains</a>. They are arranged into a heterotetramer. Thalassaemia patients produce a deficiency of either α or β globin, unlike sickle-cell disease, which produces a specific mutant form of β globin.</p><p>The thalassemias are classified according to which chain of the haemoglobin molecule is affected. In α thalassemias, production of the α globin chain is reduced, while in β thalassemia production of the β globin chain is reduced.</p><p>The β globin chains are encoded by a single gene on chromosome 11; α globin chains are encoded by two closely linked genes on chromosome 16. Thus, in a normal person with two copies of each chromosome, there are two loci encoding the β chain, and four loci encoding the α chain. Deletion of one of the α loci has a high prevalence in people of African or Asian descent, making them more likely to develop α thalassemias. β thalassemias are common in Africans, but also in Greeks and Italians.</p><p>The <a href="/articles/thalassemia-trait">thalassaemia trait</a> may confer a degree of protection against malaria, which confers a selective survival advantage on carriers.</p><h4>Radiographic features</h4><h5>Skeletal</h5><p>Marrow proliferation consists of expansion of the medulla, thinning of <a href="/articles/cortical-bone">cortical bone</a>, and resorption of <a href="/articles/cancellous-bone">cancellous bone</a> resulting in a generalized loss of bone density.</p><ul>
- +<li>skull: classic "<a href="/articles/hair-on-end-sign-mnemonic">hair-on-end</a>" appearance</li>
-<a title="Osteoporosis" href="/articles/osteoporosis-3">osteoporosis</a><sup> 4</sup>- +<a href="/articles/osteoporosis-3">osteoporosis</a><sup> 4</sup>
-</ul>- +</ul><h4>History and etymology</h4><p>Named for the the Greek word for "sea" (θάλασσα - thálassa), Cooley and Lee described bone abnormalities and severe anemia with associated splenomegaly in 1921 <sup>5</sup>.</p>
References changed:
- 5. Cooley T. Anemia in Children. Am J Dis Child. 1927;34(3):347. <a href="https://doi.org/10.1001/archpedi.1927.04130210022002">doi:10.1001/archpedi.1927.04130210022002</a>