Thalassemia

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.

Pathology

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.

Radiographic features

Skeletal

Marrow proliferation consists of an expansion of the medulla, thinning of cortical bone, and resorption of cancellous bone resulting in a generalized loss of bone density and yellow-to-red bone marrow reconversion.

• skull: the occipital bone is spared, due to lack of hemopoietic bone marrow ⁶
  • hair-on-end appearance (classic)
  • widening of the diploic space
  • thinning of the inner and outer table
• facial bones
  • rodent or chipmunk facies
  • 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
• ribs: rib-within-a-rib appearance, noted particularly in the middle and anterior portions of the ribs
• extremities: widening/expansion of the metacarpal and metatarsal shafts

• Erlenmeyer flask deformity

• premature fusion of the epiphyses
• osteoporosis ⁴
• extramedullary hematopoiesis

Gastrointestinal: hepatobiliary

• cholelithiasis
• hemosiderosis
• splenomegaly

Lung

• diffusion impairment
• air-trapping ⁷

History and etymology

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.