The genetic mutation of β thalassaemia leads to a decreased rate of β-chain synthesis and consequently a reduction in the amount of normal Hb-A in the red cell. A microcytic hypochromic anaemia results. On the basis of the extent of reduction of β-chain synthesis, two main types of β thalassaemia are recognized. β+ thalassaemia is characterized by incomplete suppression and β° thalassaemia by complete absence of chain synthesis. Both β° and β+ types occur throughout the Mediterranean region. β° thalassaemia predominates in south-east Asia, and β+ is the usual type in Blacks. Although the two types cannot always be distinguishes on clinical grounds in individual patients, the variable serverity of β thalassaemia in some population groups is ascribed in part to the existence of these two thalassaemia genes.
At the clinical level, β thalassaemia occurs classically in two forms. Beta thalassaemia major, or Cooley’s anaemia is usually a severe illness characterized by major or total suppression of chain synthesis and is the homozygous form of the disease. Beta thalassaemia minor or trait is a mild and sometimes asymptomatic condition and represents the heterozygous form. Suppression of β- chain synthesis is much less severe.
Some patients do not fit easily into these two clear-cut clinical categories. Patients may be clinically classified as thalassaemia intermedia if the severity of their disease lies between that of the major and minor forms. Thalassaemia intermedia encompasses a range of interactions between many different thalassaemia genes which result in milder defects of β-chain synthesis and globin-chain imbalance than occur in classical β thalassaemia major.
Beta thalassaemia minor (trait)
This disorder is the heterozygous state for the β thalassaemia gene. It is characterized by a moderate reduction in β-chain synthesis as directed by a β thalassaemia gene inherited from one parent. The disorder is relatively common, e.g. it has been found in eight percent of Greeks and five percent of Italians in Australia. Clinically, it is usually a very mild disorder with little or no anaemia, no symptoms and a normal life expectancy. The spleen may be palpable. The condition is commonly not diagnosed until adolescence or audit life and may be detected in a routine haematological screening examination. It is often first diagnosed in pregnancy.
Estimation of the serum iron, ferritin and transferrin and of the red cell Hb-A₂ and Hb-F usually provides a definitive diagnosis. When iron deficiency develops in a patient with thalassaemia minor, the elevated Hb-A₂ usually falls to normal but returns to a super normal level when iron stores are replenished. If the Hb-A₂ and the Hb-F levels are normal and the patient is not iron deficient the possibility of α thalassaemia should be considered and the test for Hb-H inclusions performed.
Treatment is generally not required in mild cases, and the benign nature of the disorder should be emphasized to the patient. Careful surveillance of the haemoglobin level during pregnancy is advisable and prophylactic folic acid should be given. Although a patient with thalassaemia minor may become iron deficient, it is more usual for patients to receive oral or parenteral iron therapy for many years on the mistaken assumption that all hypochromic anaemias are due to iron deficiency. Thus, it is important to inform the patient of the diagnosis and the possible harmful effects of over-enthusiastic iron therapy.
Beta thalassaemia Major
Beta thalassaemia major is the homozygous state for either the β° or β+ thalassaemia gene or less commonly, the compound heterozygous state for the two genes. In its usual form in Italian or Greek patients, it is a severe disease which often results in death during childhood unless frequent blood transfusions are given. About one in every ten patients has a mild form which is compatible with sruvival into adult life with only occasional transfusions. This form of the disorder may be referred to as thalassaemia intermedia, although the haemoglobin constitution is usually identical to that seen in classical thalassaemia major. Extreme examples of the mild form, which sometimes occur in American Blacks, are completely symptomless or have only a mild anaemia. In some cases, the clinical heterogeneity appears to be due to the interaction of other genetic (for example, α thalassaemia or hereditary persistence of fetal haemoglobin) or environmental factors with the β thalassaemia gene.
The newborn infant with β thalassaemia major is not anaemic. The onset of anaemia is insidious, the initial manifestation being pallor, which is usually obvious within the first year of life and in severe cases within a few weeks of birth. Subsequent prognosis depends on whether the child is entered into a programme of regular blood transfusions. If the disorder take this natural course without active therapytic intervention, growth and development in early childhood are retarded. The child fails to thrive, and anorexia, diarrhoea, loss of body fat, and recurrent fever occur. The severe anaemia usually results in cardiac dilatation. Splenomegaly is obvious by the age of three years and the large spleen causes abdominal swelling and discomfort and symptoms due to pressure on surrounding organs. Moderate to marked hepatomegaly is also present. Beta thalassemia affected patients lead their life in different kinds of abnormality. Such as skeletal system changes, pathological fractures, bone pain, impairment of growth, epistaxis, skin pigmentation, leg ulcers, gall stones etc.
Most patients with β thalassaemia major are severely anaemic and many of the distressing symptoms of the condition are directly related to the anaemia. The compensatory mechanisms recruited by the body to improve the production of viable red cells may also cause symtoms, and in some patients are more troublesome than the anaemia itself. The expanding hyperplastic bone marrow leads to gross skeletal changes, particularly affecting the face; masses of extramedullary erythroid tissue compress vital structures; and increased iron absorption cause deposition of iron in parenchymal tissues. Thus, blood transfusion which alleviates the anaemia and suppresses the compensatory mechanisms is the basis of therapy.
In order to prevent the inevitable accumulation of iron, the iron-chelating agent desferrioxamine (DF) is used. DF is able to remove substantial amounts of storage iron via urine and stool and if commenced early of life preferably at the same time as the regular transfusion regimen, will prevent the occurrence of iron overload.
Splenectomy should not be performed, if at all possible, until the age of five or six years. There is a major risk of life-threatening infection in children who are splenectomized before this age. The reasons for the increased susceptibility to infection following removal of the spleen are not known with certainty, but are probably similar to those in sickel-cell disease. Pneumococcus, meningococcus and haemophilus influenzae are usually the organisms involved. Immunization with plyvalent pneumococcal vaccine is essential, and most authorities recommend prophylactic oral penicillin.