Thalassemia D56.8

• Thalassaemia major: predominantly homozygous β thalassemia (Cooley's anemia) or mixed heterozygous β thalassemia with transfusion dependence.
• Thalassaemia minor: heterozygous β thalassemia.
• Thalassaemia intermedia: predominantly homozygous or mixed heterozygous β thalassemia with additional genetic alterations that lead to a reduction of the symptoms typical of thalassaemia major.

• Mediterranean region (Malta, Sardinia, Sicily, Greece, Cyprus), in the Middle East and among the population of African origin.
• The β thalassemia is the most common form of thalassemia. Over 4000 mutations are known to occur.

• Autosomal recessive inheritance.

  Notice! A special feature of recessive hereditary disorders is a defined heterozygote symptomatology: heterozygote mutation carriers are affected by a clinically mostly mild anemia (thalassaemia minor), while homozygote carriers show the severe full picture of thalassemia major with organ complications.

• β thalassemia: smaller grid or point mutations at the β globin locus; rarely longer deletions. Thus reduction or absence of the β-globin. In Cooley's anemia no normal HbA is formed. The strong excess of γ and δ globins leads to defective, unstable erythrocytes with ineffective erythropoiesis.
• α thalassemia: missing α chains, resulting in an excess of γ and β globins.

• Thalassaemia minor (heterozygous β thalassaemia): mostly no clinical symptoms, possibly slightly enlarged spleen, dystrophic hair and effluvium, dizzy spells
• Thalassaemia major (homozygous β thalassemia [Cooley's anemia]): already a few months post partum approaches of hepato- or splenomegaly. In the course of the disease: disturbances of growth and development, severe damage to internal organs and bone malformations. Severe disorders of erythrocytopoiesis with severe anemia and consecutive severe hemosiderosis. Lifelong need for transfusion. Untreated in infancy or early childhood lethal.

• Blood work with hypochromic, microcytic anemia, target cells.
• Serum: elevated serum iron, elevated ferritin.
• Hb electrophoresis.
• Molecular genetic analysis.

Thalassaemia major: symptomatic therapy with blood transfusions (so-called hypertransfusion regime): 1-3 blood units every 2-3 weeks with the aim of suppressing the patient's own ineffective erythropoiesis, splenectomy if necessary (as late as possible due to the increased risk of bacterial infection). Due to iron overload, chelation with desferrioxamine or deferiprone (Ferriprox) is necessary. Stem cell or bone marrow transplantation if necessary.

Thalassaemia minor: no therapy required (exception: pregnancy).

1. Cario H, Stahnke K, Sander S, Kohne E (2000) Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter beta-thalassemia study. Ann Hematol 79: 7-12
2. Maggio A, D'Amico G, Morabito A (2004) Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial. Blood Cells Mol Dis 32: 141-142