Thalassaemia is an autosomal recessive haemoglobinopathy 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.
Thalassemia is a quantitative problem of globin synthesis, whereas sickle-cell disease is a qualitative problem of synthesis of an incorrectly functioning globin.
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 δ globin 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.
- 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
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.
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