I. Disease
Thalassemias are a group of genetic disorders characterized by an abnormality in the synthesis of the globin chains, compounds of the hemoglobin (oxygen-transport protein). Hemoglobin (Hb) is normally composed by :
- 97 % Hb A (2 α chains and 2 β chains)
- 2-3 % Hb A2 (2 α chains and 2 δ chains)
- < 1 % Hb F (2 α chains and 2 γ chains)
Bêta thalassemia is characterised by an absence (bêta0) or a reduction (bêta+) of the of β chains synthesis.
II. Epidemiology
Bêta thalassemia is very frequent between the Mediterranean basin populations, North Africa, South-East Asia, India and China.
III. Clinical signs
The β-globin being produced only after birth, the disease does not appear before 2-6 months. The main clinical sign is a severe anemia. It is also observed a hepatosplenomegalia (increase in the liver and the spleen volume), and an abnormal morphology of the skull and the face. At adolescence, some troubles on the synthesis of the bone tissue appear (ostopenia), accompanied by slowed growth and delayed puberty, which will evolve into osteoporosis. The evolution of the homozygot disease can bring to complications such as: leg ulcers, haemochromatosis (iron overload) related to blood transfusions, biliary lithiaisis, (stones in the gall bladder), heard rate troubles, secondary infection.
IV. Genetics
Bêta thalassemia is a hereditary disease (recessive autosomal transmission, linked to a mutation in the bêta globin gene located in chromosome 11. Around 200 mutations have been described. Individuals presenting a mutation of the β-globin on a copy of chromosome 11 (heterozygote’s) present a minor β-thalassemia, resulting in a very moderated or even absent anaemia, with no need of clinical care. Individuals in which both copies of the chromosome present a mutation of the β-globin develop a major β-thalassemia (Cooley anaemia), or a less serious affection, the intermediate β-thalassemia.
V. Diagnosis
In the laboratory, we observe a microcitary anemia (reduction on the red globule volume), hypochrome (decrease in Hb level). The spinal cord biopsy shows a hyperplastic marrow, very rich in immature red blood cells (erythroblasts).Electrophoresis of proteins shows the presence of Hb F up to 90% and A2 from 5 to 20%.
VI. Prenatal diagnosis
A prenatal diagnosis is possible and it should be proposed to at-risk couples (when both parents are heterozygote) or couples having already an affected child. The analysis can be done from different kind of samples: a) chorionic villi (throphoblastic tissue) from 11 weeks of amenorrhea or b) amniocytes obtained by amniocentesis from 14 weeks of amenorrhea.
VII. Genetic analysis – Technique
Biological sample: saliva on FTA cardAnalysis of the following mutations: Study of the entire gene (HBB)Analysis description: PCR + sequencing of the entire gene, including 5’ end
VIII. Treatment
The treatment consists essentially on blood transfusions, in order to maintain a sufficient level of Hb. The major risk is related to the apparition of a secondary hemochromatosis. Besides the transfusions, the treatment is based on :
- splenectomy (removal of the spleen)
- correcting of associated deficiencies (intake of folates, zinc, vitamin C, vitamin E)
- pneumococcal vaccination (in case of splenectomy)
- prevention of secondary hemochromatosis
- low iron diet