analysis is available but is not routinely done. What is it? • Haemoglobin H Disease (3 affected genes). With this Thalassaemia is a group of inherited disorders that affect condition, the large decrease in the amount of alpha globin the amount of haemoglobin a person produces. chains produced causes an excess of beta chains which then Haemoglobin refers to a family of compounds all made up of aggregate into beta4 tetramers (groups of 4 beta chains), haem (an iron-containing complex), and various globins known as Haemoglobin H. HbH disease can cause moderate to (protein chains that surround the haem complex). severe Anaemia and splenomegaly (enlarged spleen). The Haemoglobin (Hb) molecules are found in all red blood cells, clinical picture associated with HbH disease is extremely and are the reason for their red colour. They bind oxygen in the variable, however. Some individuals are asymptomatic while lungs, carry it through the bloodstream, and release it to the others have severe Anaemia. Haemoglobin H disease is found body’s tissues. most often in individuals of Southeast Asian or Eastern Normal adult haemoglobins include: Mediterranean descent. • Haemoglobin A (about 95% - 98%). HbA contains two • Alpha Thalassaemia Major (also called hydrops fetalis, 4 affected genes). This is the most severe form of alpha alpha (α) chains and two beta (ß) chains. thalassaemia. In this condition, no alpha globin is produced, • HbA2 (about 2% - 3.5%), has two alpha (α) and two delta therefore, no HbA or HbF are produced. Fetuses affected by (δ) chains alpha thalassaemia major become anemic early in pregnancy. • HbF (up to 2%). This is the primary haemoglobin They become hydropic (retain fluids), and frequently have produced by the fetus during gestation. Its production enlarged hearts and livers. This diagnosis is frequently made in usually falls to a low level within a year after birth. HbF the last months of pregnancy when a fetal ultrasound indicates has two alpha (α) and two gamma (γ) chains. a hydropic fetus. About 80% of the time the mother will have Mutations in the genes coding for the globin chains can cause toxaemia and can develop severe postpartum hemorrhage. disorders in haemoglobin production. There are 4 genes coding Fetuses with alpha thalassaemia major are usually miscarried, for alpha globin chains and 2 genes coding for the beta globin stillborn, or die shortly after birth. chains. Inherited disorders of haemoglobin production fall into two Individuals with alpha thalassaemia may be misdiagnosed as categories: iron deficient by unwary doctors, as iron deficiency also leads to • Thalassaemia: decreased production of normal small pale (microcytic hypochromic) red cells. It is important haemoglobins that iron therapy in thalassaemic patients is only given when specific iron tests (LINK TO FERRITIN, SERUM IRON, TIBC • Haemoglobinopathy: production of an abnormal &TRANSFERRIN) have confirmed iron deficiency. This is haemoglobin molecule especially important in alpha thalassaemia, where there is a Thalassaemias are a group of disorders in which mutations in small potential for dangerous iron overload to develop. one or more of the alpha or beta globin genes cause a Alpha thalassaemia is found most commonly in individuals with reduction in the amount of the HbA produced. This leads to a an ethnic background of Southeast Asia, Southern China, the reduction in HbA, the relative increase in the amount of minor Middle East, India, Africa and the Mediterranean. haemoglobins HbA2 and HbF, and perhaps detection of unusual haemoglobin types. Beta thalassaemia The thalassaemias are usually classified by the type of globin is due to mutations, in one or both of the beta globin genes. chain whose synthesis is reduced. There are 100 to 200 mutations that have been identified but Thalassaemia Classifications only about 20 are common. The severity of the Anaemia caused Alpha thalassaemia by beta thalassaemia depends on which mutations are present is due to a deletion or mutation in one or more of the 4 alpha and on whether they decrease beta globin production (called globin gene copies. The more genes affected, the less alpha beta+ thalassaemia) or completely eliminate it (called beta0 globin produced. The four different types of alpha thalassaemia thalassaemia). The different types of beta thalassaemia include: include: • Silent Carrier State (1 affected gene). The silent carrier • Beta Thalassaemia Trait. A person with this condition has will have normal haemoglobin levels red cell indices which are one normal gene and one with a mutation. They will usually normal or show a slightly decreased MCH (hypochromia). experience no health problems other than microcytosis (small Carriers can pass on the affected gene to their offspring. Often red blood cells) and a possible mild Anaemia that will not these individuals are identified only after having a child with respond to iron supplements. This gene mutation can be passed HbH disease or alpha thalassaemia trait. on to an individual’s children. • Alpha Thalassaemia Trait (2 affected genes). Patients • Thalassaemia Intermedia. In this condition, an affected who have alpha thalassaemia trait have smaller (microcytic), person has two abnormal genes but is still producing some beta paler (hypochromic) red blood cells and a mild chronic Anaemia globin. The severity of the Anaemia and health problems but do not generally experience any symptoms. This is an experienced depends on the mutations present. The dividing Anaemia that does not respond to iron supplements. Diagnosis line between thalassaemia intermedia and thalassaemia major of alpha thalassaemia trait is usually by exclusion of other 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 deficiency is causing and/or exacerbating a patient’s them on a regular basis. Anaemia. One or more of them may also be ordered to • Thalassaemia Major (also called Cooley's Anaemia). help monitor the degree of iron overload in a patient with This is the most severe form of beta thalassaemia. The patient thalassaemia. has two abnormal genes that cause either a severe decrease or 4. Haemoglobinopathy (Hb) evaluation. This test complete lack of beta globin production, preventing the measures the type and relative amounts of production of significant amounts of HbA. This condition usually haemoglobins present in the red blood cells. appears in an infant after 3 months of age and causes life- Haemoglobin A, composed of both alpha and beta threatening Anaemia. This Anaemia requires lifelong regular globin, is the major normal type of haemoglobin found blood transfusions and considerable ongoing medical care. Over in adults. A greater percentage of HbA2 and/or HbF is time these frequent transfusions lead to excessive amounts of usually seen in beta thalassaemia trait. HbH may be iron in the body. Left untreated, this excess iron can deposit seen in alpha thalassaemia , but only when at two of into the liver, heart and other organs, and can lead to a the four alpha genes are deleted or mutated. premature death from organ failure. 5. DNA analysis. This test is used to investigate deletions Other forms of thalassaemia occur when a gene for beta and mutations in the alpha and beta globin producing thalassaemia is inherited in combination with a gene for a genes. Family studies can be done to evaluate carrier haemoglobin variant. (link to Hb Variant page) The most status and the types of mutations present in other important of these are: family members. DNA testing is not routinely done but • HbE – beta thalassaemia. HbE is one of the most can be used to help diagnose thalassaemia, and to common haemoglobin variants, found predominantly in people determine carrier status. It is the only reliable way of of Southeast Asian descent. If a person inherits one HbE gene diagnosing carriers who have only one of four alpha and one beta thalassaemia gene, the combination produces genes deleted or mutated. 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. Laboratory Tests 1. FBC (full blood count). The FBC is a snapshot of the cells and fluid in your bloodstream. Among other things, the FBC will tell the doctor how many red blood cells are present, how much haemoglobin is in them, and give the doctor an evaluation of the size and shape of the red blood cells present. MCH (mean corpuscular haemoglobin) and MCV (mean corpuscular volume) are measurements of the haemoglobin content and size of the red blood cells. A low MCH or MCV is often the first indication of thalassaemia. If the MCH or MCV is low and iron-deficiency has been ruled out, the person may be a thalassaemia trait carrier. 2. Blood film (smear). In this test a thin stained layer of blood is examined on a slide, under a microscope. The number and type of white blood cells, red blood cells, and platelets can be manually counted and be evaluated to see if they are normal and mature. A variety of disorders affect normal blood cell production. With thalassaemia, the red blood cells are often microcytic (small). They may also be: • Hypochromic (pale – indicating less haemoglobin) • Vary in size (anisocytosis) and shape (poikilocytosis) • Be nucleated (not normal in a mature RBC) • Be distorted to produce “target cells”, which look like a bull’s-eye under the microscope. 3. Iron studies. These may include: Iron, Ferritin, UIBC, TIBC, and Percent Saturation of Transferrin. These tests measure different aspects of the body’s iron storage and usage. They are ordered to help determine whether an iron