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Alpha thalassaemia is due to a deletion or mutation in one or more of the 4 alpha globin gene copies. The more genes affected, the less alpha globin produced. The four different types of alpha thalassaemia include:
- Alpha thalassaemia trait (1 affected gene). The silent carrier will have normal haemoglobin levels and red cell indices which are normal or show a slightly decreased MCH (hypochromia). Carriers can pass on the affected gene to their offspring. Often these individuals are identified only after having a child with HbH disease or alpha thalassaemia trait.
- Alpha thalassaemia trait (2 affected genes). Patients who have alpha thalassaemia trait have smaller (), paler () red blood cells and a mild chronic anaemia but do not generally experience any symptoms. This is an anaemia that does not respond to iron supplements. Diagnosis of alpha thalassaemia trait is usually by exclusion of other causes of microcytic anaemia. Confirmatory testing by DNA analysis is an important part of the testing process for Alpha thalassaemia because there are two copies (HbA1 and HbA2) of the alpha-chain gene on each chromosome. If the person has lost both copies from one chromosome this has different implications for passing on a more serious form of the disease to their children than if they have lost one copy from each of the two different chromosome. See the section on DNA analysis below.
- Haemoglobin H disease (3 affected genes). With this condition, the large decrease in the amount of alpha globin chains produced causes an excess of beta chains which then aggregate into beta4 tetramers (groups of 4 beta chains), known as haemoglobin H. HbH disease can cause moderate to severe anaemia and splenomegaly (enlarged spleen). The clinical picture associated with HbH disease is extremely variable. Some individuals are asymptomatic while others have severe anaemia. Haemoglobin H disease is found most often in individuals of Southeast Asian or Eastern Mediterranean descent.
- Alpha thalassaemia major (also called hydrops fetalis, 4 affected genes). This is the most severe form of alpha thalassaemia. In this condition, no alpha globin is produced, therefore, no HbA or HbF are produced. Fetuses affected by alpha thalassaemia major become anaemic early in pregnancy. They become (retain fluids), and frequently have enlarged hearts and livers. This diagnosis is frequently made in the last months of pregnancy when a fetal ultrasound indicates a hydropic fetus. About 80% of the time the mother will have and can develop severe postpartum haemorrhage (bleeding). Fetuses with alpha thalassaemia major are usually miscarried, stillborn, or die shortly after birth.
Individuals with alpha thalassaemia may be misdiagnosed as iron deficient by unwary doctors, as iron deficiency also leads to small pale (microcytic hypochromic) red cells. It is important that iron therapy in thalassaemic patients is only given when specific iron tests (ferritin, serum iron, TIBC, transferrin) have confirmed iron deficiency. This is especially important in alpha thalassaemia, where there is a small potential for dangerous iron overload to develop.
Alpha thalassaemia is found most commonly in individuals with an ethnic background of Southeast Asia, Southern China, the Middle East, India, Africa and the Mediterranean.
Beta thalassaemia is due to mutations, in one or both of the beta globin genes. There are 100 to 200 mutations that have been identified but only about 20 are common. The severity of the anaemia caused by beta thalassaemia depends on which mutations are present and on whether they decrease beta globin production (called beta+ thalassaemia) or completely eliminate it (called beta0 thalassaemia). The different types of beta thalassaemia include:
- Beta thalassaemia trait. A person with this condition has one normal gene and one with a mutation. They will usually experience no health problems other than microcytosis (small red blood cells) and a possible mild anaemia that will not respond to iron supplements. This gene mutation can be passed on to an individual’s children.
- Thalassaemia intermedia. In this condition, an affected person has two abnormal genes but is still producing some beta globin. The severity of the anaemia and health problems experienced depends on the mutations present. The dividing line between thalassaemia intermedia and thalassaemia major is the degree of anaemia and the number and frequency of blood transfusions required to treat it. Those with thalassaemia intermedia may need occasional transfusions but do not require them on a regular basis.
- Thalassaemia major. This is the most severe form of beta thalassaemia. The patient has two abnormal genes that cause either a severe decrease or complete lack of beta globin production, preventing the production of significant amounts of HbA. This condition usually appears in an infant after 3 months of age and causes life-threatening anaemia. This anaemia requires lifelong regular blood transfusions and considerable ongoing medical care. Over time these frequent transfusions lead to excessive amounts of iron in the body. Left untreated, this excess iron can deposit into the liver, heart and other organs, and can lead to a premature death from organ failure.
Other forms of thalassaemia occur when a gene for beta thalassaemia is inherited in combination with a gene for a haemoglobin variant. The most important of these are:
- HbE – beta thalassaemia. HbE is one of the most common haemoglobin variants, found predominantly in people of Southeast Asian descent. If a person inherits one HbE gene and one beta thalassaemia gene, the combination produces HbE-beta thalassaemia which causes a moderately severe anaemia similar to beta thalassaemia intermedia.
- HbS – beta thalassaemia or sickle cell – beta thalassaemia. HbS is one of the most well known of the haemoglobin variants. Inheritance of one HbS gene and one beta thalassaemia gene results in HbS-beta thalassaemia. The severity of the condition depends on the amount of beta globin produced by the beta gene. If no beta globin is produced, the clinical picture is almost identical to sickle cell disease.
Last Review Date: November 23, 2018