Thalassaemia

Thalassaemia is the name of a group of genetic blood disorders.

To understand how thalassaemia affects the human body, you must first understand a little about how blood is made.

Haemoglobin is the oxygen-carrying component of the red blood cells. It consists of two different proteins, an alpha and a beta. If the body doesn’t produce enough of either of these two proteins, the red blood cells do not form properly and cannot carry sufficient oxygen. The result is anaemia that begins in early childhood and lasts throughout life. Since thalassaemia is not a single disorder but a group of related disorders that affect the human body in similar ways, it is important to understand the differences between the various types of thalassaemia.

People whose hemoglobin does not produce enough beta protein have beta thalassemia. 

It is found in people of Mediterranean descent, such as Italians and Greeks, and is also found in the Arabian Peninsula, Iran, Africa, Southeast Asia and southern China.

There are three types of beta thalassemia that also range from mild to severe in their effect on the body.

Thalassemia Minor or Thalassemia Trait: In this condition, the lack of beta protein is not great enough to cause problems in the normal functioning of the hemoglobin. A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anemia. As in mild alpha thalassemia, physicians often mistake the small red blood cells of the person with beta thalassemia minor as a sign of iron-deficiency anemia and incorrectly prescribe iron supplements.

Thalassemia Intermedia: In this condition the lack of beta protein in the hemoglobin is great enough to cause a moderately severe anemia and significant health problems, including bone deformities and enlargement of the spleen. However, there is a wide range in the clinical severity of this condition, and the borderline between thalassemia intermedia and the most severe form, thalassemia major, can be confusing. The deciding factor seems to be the amount of blood transfusions required by the patient. The more dependent the patient is on blood transfusions, the more likely he or she is to be classified as thalassemia major. Generally speaking, patients with thalassemia intermedia need blood transfusions to improve their quality of life, but not in order to survive.

Thalassemia Major or Cooley’s Anemia: This is the most severe form of beta thalassemia in which the complete lack of beta protein in the hemoglobin causes a life-threatening anemia that requires regular blood transfusions and extensive ongoing medical care. These extensive, lifelong blood transfusions lead to iron-overload which must be treated with chelation therapy to prevent early death from organ failure.

People whose hemoglobin does not produce enough alpha protein have alpha thalassemia. It is commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally the Mediterranean region.

There are various types of alpha thalassemia that range from mild to severe in their effect on the body.

Silent Carrier State: This condition generally causes no health problems because the lack of alpha protein is so small that the hemoglobin functions normally. It is called “silent carrier” because of how difficult it is to detect. Silent carrier state is “diagnosed” by deduction when an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia trait.

Hemoglobin Constant Spring: This is an unusual form of Silent Carrier state that is caused by a mutation of the alpha globin. It is called Constant Spring after the region of Jamaica in which it was discovered. As in silent carrier state, an individual with this condition usually experiences no related health problems.

Alpha Thalassemia Trait or Mild Alpha Thalassemia: In this condition, the lack of alpha protein is somewhat greater. Patients with this condition have smaller red blood cells and a mild anemia, although many patients do not experience symptoms. However, physicians often mistake mild alpha thalassemia for iron deficiency anemia and prescribe iron supplements that have no effect on the anemia.

Hemoglobin H Disease: In this condition, the lack of alpha protein is great enough to cause severe anemia and serious health problems such as an enlarged spleen, bone deformities and fatigue. It is named for the abnormal hemoglobin H (created by the remaining beta globin) that destroys red blood cells.

Hemoglobin H-Constant Spring: This condition is more severe than hemoglobin H disease. Individuals with this condition tend to have a more severe anemia and suffer more frequently from enlargement of the spleen and viral infections. Homozygous Constant Spring. This condition is a variation of hemoglobin H-Constant Spring that occurs when two Constant Spring carriers pass their genes on to their child (as opposed to hemoglobin H Constant Spring, in which one parent is a Constant Spring Carrier and the other a carrier of alpha thalassemia trait). This condition is generally less severe than hemoglobin H Constant Spring and more similar to hemoglobin H disease.

Hydrops Fetalis or Alpha Thalassemia Major: In this condition, there are no alpha genes in the individual’s DNA, which causes the gamma globins produced by the fetus to form an abnormal hemoglobin called hemoglobin Barts. Most individuals with this condition die before or shortly after birth. In some extremely rare cases where the condition is discovered before birth, in utero blood transfusions have allowed the birth of children with hydrops fetalis who then require lifelong blood transfusions and medical care.

In addition to the alpha and beta thalassemias, there are other related disorders that occur when the gene for alpha or beta thalassemia combines with an abnormal or mutant gene.

E Beta Thalassemia: Hemoglobin E is one of the most common abnormal hemoglobins. It is usually found in people of Southeast Asian ancestry, such as Cambodians, Vietnamese and Thai. When combined with beta thalassemia, hemoglobin E produces E beta thalassemia, a moderately severe anemia which is similar in symptoms to beta thalassemia intermedia.

Sickle Beta Thalassemia: This condition is caused by a combination of beta thalassemia and hemoglobin S (Hb S), the abnormal hemoglobin found in people with sickle cell disease. It is commonly found in people of Mediterranean ancestry, such as Italians, Greeks and Turks. The condition varies according to the amount of normal beta globin produced by the beta gene. When no beta globin is produced by the beta gene, the condition is almost identical with sickle cell disease. The more beta globin produced by the beta gene, the less severe the condition. Source: http://www.thalassemia.org/ 

Sickle Cell Anaemia

The disorder affects the red blood cells which contain a special protein called haemoglobin (Hb for short). The function of haemoglobin is to carry oxygen from the lungs to all parts of the body.

People with SICKLE CELL ANAEMIA have Sickle haemoglobin (HbS) which is different from the normal haemoglobin (HbA). When sickle haemoglobin gives up its oxygen to the tissues, it sticks together to form long rods inside the red blood cells making these cells rigid and sickle-shaped. Normal red blood cells can bend and flex easily.

Because of their shape, sickled red blood cells can’t squeeze through small blood vessels as easily as the almost donut-shaped normal cells. This can lead to these small blood vessels getting blocked which then stops the oxygen from getting through to where it is needed. This in turn can lead to severe pain and damage to organs.

Everyone has two copies of the gene for haemoglobin; one from their mother and one from their father. If one of these genes carries the instructions to make sickle haemoglobin (HbS) and the other carries the instructions to make normal haemoglobin (HbA) then the person has Sickle Cell Trait and is a carrier of the sickle haemoglobin gene. This means that this person has enough normal haemoglobin in their red blood cells to keep the cells flexible and they don’t have the symptoms of the sickle cell disorders. They do however have to be careful when doing things where there is less oxygen than normal such as scuba diving, activities at high altitude and under general anaesthetics.

If both copies of the haemoglobin gene carry instructions to make sickle haemoglobin then this will be the only type of haemoglobin they can make and sickled cells can occur. These people have Sickle Cell Anaemia and can suffer from anaemia and severe pain. These intense and severe attacks are known as Crises. Over time Sickle Cell sufferers can experience damage to organs such as liver, kidney, lungs, heart and spleen. Death can be an outocme of the disorder.

Another problem is that red blood cells containing sickle haemoglobin do not live as long as the normal 120 days and this results in a chronic state of anaemia. In spite of this, a person with sickle cell disorder can attend school, college and work. People with sickle cell disorder need regular medical attention particularly before and after operations, dental extraction and during pregnancy. Many hospitals arrange follow-up appointments and it is advisable to discuss with the doctors questions concerning schooling, strenuous exercise, family planning, suitable types of employment and air travel. When a person is found to have a sickle cell disorder it is important that all members of the family be tested. They will not necessarily have sickle cell disorder but may be healthy carriers of a sickle cell trait.

There are also other different types of haemoglobin such as HbC and beta thalassaemia, that can combine with sickle haemoglobin to cause sickling disorders. When someone carries the gene for beta-thalassaemia they cannot make as much HbA as they should. If this is combined with the HbS gene then more of their total amount of haemoglobin is HbS and they can suffer from what is usually a milder form of sickle cell disorder than sickle cell anaemia.

The different kinds of SCD and the different traits are found mainly in people whose families come from Africa, the Caribbean, the Eastern Mediterranean, Middle East and Asia.* In Britain SCD is most common in people of African and Caribbean descent. It is estimated there are more than 15,000 adults and children with SCD in Britain at present. Every year about 350 babies are born with SCD. There are other inherited conditions that mainly affect other groups, e.g. Cystic Fibrosis in Europeans, and Tay-Sachs disease in Jewish people.

People are often confused and disturbed by some of the incorrect information they have received about SCD. Sickle Cell Disorders

– are not leukaemia / are not cancer / are not white blood cells eating up red blood cells
– are not infectious – you cannot `catch it’ as you would catch measles or a cold

Sickle Cell Disorder is a condition which is inherited from both parents. This means that people are born with it, just as they are born with other characteristics such as eye colour, hair texture and height.

Information from: Sickle Cell Society UK – http://www.sicklecellsociety.org/resources/what-is-sickle-cell-anaemia/

Sickle cell trait is an inherited blood disorder that affects 1 million to 3 million Americans and 8 to 10 percent of African Americans. Sickle cell trait can also affect Hispanics, South Asians, Caucasians from southern Europe, and people from Middle Eastern countries. More than 100 million people worldwide have sickle cell trait.

Unlike sickle cell disease, a serious illness in which patients have two genes that cause the production of abnormal hemoglobin (the substance in red blood cells that helps carry oxygen), individuals with sickle cell trait carry only one defective gene and typically live normal lives. Rarely, extreme conditions such as severe dehydration and high-intensity physical activity can lead to serious health issues, including sudden death, for individuals with sickle cell trait.

 – If an individual has sickle cell trait, it means that he/she has inherited (carries) a single copy of the gene that causes sickle cell disease. It is NOT a disease.

 – Sickle cell trait can never become sickle cell disease.

In general, people with sickle cell trait enjoy normal life spans with few medical problems related to sickle cell trait. It is possible, however, for individuals with sickle cell trait to pass the gene to their children.

Information from the American Society of Hematology – ​http://www.hematology.org/Patients/Anemia/Sickle-Cell-Trait.aspx

The Thalassaemia Society of NSW recommends testing. A special blood test (haemoglobin electrophoresis) can tell you whether you have a sickle cell disorder or are a healthy carrier, e.g. for sickle cell trait. Routine screening should take place for all pregnant women, all newborn babies, and before anaesthesia, either at hospital or dental clinics.

When both parents carry a genetic trait for a haemoglobin disorder, there is a 25% risk that their child will inherit the full disorder, which requires life-long treatment.