Last revised by Rohit Sharma on 20 May 2024

Thalassemia is an autosomal recessive hemoglobinopathy 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 hemoglobin molecules. The resultant microcytic anemia is the characteristic presenting symptom of the thalassemias.

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 hemoglobin is composed of HbA (98%) and HbA2 (2%). HbA contains two α globin chains and two β globin chains, and HbA2 contains two α globin chains and two δ globin chains. They are arranged into a heterotetramer. Thalassemia 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 hemoglobin 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 thalassemia trait may confer a degree of protection against malaria, which confers a selective survival advantage on carriers.

Ineffective hematopoiesis results in severe anemia that in turn leads to an increase in erythropoietin. This increase results in an expansion of the bone marrow by a factor of up to 15 to 30 9. Conversion of yellow to red marrow occurs and in patients with uncontrolled disease marrow expansion results in an enlargement of the medullary space and thinning of cortical bone 8

This expansion leads to the destruction of medullary trabeculae with initial cortical and trabecular thinning leading to a subsequent coarsening appearance that may even lead to a "cob-webbing" pattern 9

  • osteoporosis and osteopenia 4,8

  • extramedullary hematopoiesis may appear as lobulated masses covering the anterior or posterior segments of the ribs on chest x-ray; extramedullary hematopoiesis is also more frequently seen in the posterior mediastinum compared to the anterior mediastinum or the pelvis 8

  • growth restriction 9

  • older patients tend to have signs of marrow proliferation in the axial skeleton with appendicular skeletal changes from early life regressing or completely disappearing 8

  • rodent or chipmunk facies due to lateral displacement of the orbits (hypertelorism) with maxillary protrusion and ventral displacement of the incisors 8

  • hypopneumatisation of the frontal, maxillary, and sphenoid sinuses, filled with marrow containing bone 6

  • the ethmoid sinuses are spared due to lack of red bone marrow 6

  • dental malocclusion

  • expansion of the ribs: especially at the costovertebral junctions 8

  • rib-within-a-rib appearance, noted particularly in the middle and anterior portions of the ribs 8,9

  • an initial increase in height to width ratio of vertebral bodies 9

  • gradual loss of height and biconcavity secondary to compression fractures 9

  • severe degree of medullary expansion can cause compression of the spinal cord in the thoracic region 8

  • scoliosis 

  • widening/expansion of the metacarpal and metatarsal shafts

  • premature fusion of the epiphyses 8,9

  • reduce longitudinal growth of long bones (humerus more than femur) 9

  • loss of concave shape in the long bones resulting in a convex shape 8

  • coarsening of the trabecular bone with cyst-like lucencies leading to a "worm-eaten" appearance 8

  • enlargement of nutrient foramina due to the activity of hyperplastic marrow 8,9

  • Erlenmeyer flask deformity

  • Harris lines

Named for the Greek word for "sea" (θάλασσα - thálassa) as the condition is more prevalent in those living around the Mediterranean Sea e.g. Italians, Greeks, etc. Cooley and Lee described bone abnormalities and severe anemia with associated splenomegaly in 1921 5.

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