What are the thalassemias?

What are the thalassemias?

The thalassemias are a group of genetic (inherited) blood disorders that share in common one feature, the defective production of hemoglobin, the protein that enables red blood cells to carry oxygen (and carbon dioxide). There are many different disorders with defective hemoglobin synthesis and, hence, many types of thalassemia.

What is beta thalassemia?

The most familiar type of thalassemia is beta thalassemia. It involves decreased production of normal adult hemoglobin (Hb A), the predominant type of hemoglobin from soon after birth until death. (All hemoglobin consists of two parts: heme and globin). The globin part of Hb A has 4 protein sections called polypeptide chains. Two of these chains are identical and are designated the alpha chains. The other two chains are also identical to one another but differ from the alpha chains and are termed the beta chains. In persons with beta thalassemia, there is reduced or absent production of beta globin chains.

What is the difference between thalassemia minor and major?

There are two forms of beta thalassemia. They are thalassemia minor and thalassemia major (which is also called Cooley's anemia).

Thalassemia minor: The individual with thalassemia minor has only one copy of the beta thalassemia gene (together with one perfectly normal beta-chain gene). The person is said to be heterozygous for beta thalassemia.

Persons with thalassemia minor have (at most) mild anemia (with slight lowering of the hemoglobin level in the blood). This situation can very closely resemble that with mild iron-deficiency anemia. However, persons with thalassemia minor have a normal blood iron level (unless they have are iron deficient for other reasons). No treatment is necessary for thalassemia minor. In particular, iron is neither necessary nor advised.

Thalassemia major (Cooley's anemia): The child born with thalassemia major has two genes for beta thalassemia and no normal beta-chain gene. The child is homozygous for beta thalassemia. This causes a striking deficiency in beta chain production and in the production of Hb A. Thalassemia major is, therefore, a serious disease.

The clinical picture associated with thalassemia major was first described in 1925 by the American pediatrician Thomas Cooley. Hence, the name Cooley's anemia in his honor.

At birth the baby with thalassemia major seems entirely normal. This is because the predominant hemoglobin at birth is still fetal hemoglobin (Hb F). Hb F has two alpha chains (like Hb A) and two gamma chains (unlike Hb A). It has no beta chains so the baby is protected at birth from the effects of thalassemia major.

Anemia begins to develop within the first months after birth. It becomes progressively more and more severe. The infant fails to thrive (to grow normally) and often has problems feeding (due to easy fatigue from lack of oxygen, with the profound anemia), bouts of fever (due to infections to which the severe anemia predisposes the child) and diarrhea and other intestinal problems.

Thalassemia major- chipmunk facies

Beta Thalassemia

Thalassemia Major Exjade

Ahmedabad doctorshave carried out a rare successful stem cell transplant on a four-year-old girl suffering from Thalassemia major, relieving her of life-long blood transfusions.

Isha Gohel from Saurastra, who was diagnosed of suffering from advanced stages of Thalassemia, had started receiving blood transfusions at the age of 18 months.

When she was brought to Apollo hospital in Ahmedabad, doctors after investigations found that she was a case of class 3 Thalassemia Major. Since she did not get good quality blood transfusion, her condition was very poor. She had developed marked enlargement of the spleen leading to further poor response to blood transfusions.

Terming Isha's case as challenging, Dr Chirag A Shah, haematologist, Apollo hospital here, said that they followed the style of treatment of Dr G Lucarelli from the Mediterranean Institute of Haematology – an international centre for transplantation in thalassemia and Sickle Cell Anaemia – in Italy who has successfully treated advanced cases of thalassemia.

Her spleen was removed and stems cells from Isha's two-year-old brother were transplanted. "We followed his (Lucarelli's) formulae for treatment of Isha and we were successful," he said.

"Stemcell transplant in advanced cases of thalassemia results in poor outcome. Such patients are not advised a transplant as they frequently have poor results and have high risk of complications," Shah said.

He said that Isha's case was difficult for them as her spleen had blown out of proportion and her liver too was damaged due to iron deposits.

Giving details of her treatment, he said, "We first surgically removed her spleen in January and the following month we started on a special protocol of medicines to reduce her risk of being Class 3. This continued for over one month until finally she underwent stem cell transplant procedure in April. The stem cells were from her younger brother."

Isha is now on the road to recovery and and will be transfusion free forever as her underlying Thalassemia major is now cured after stem cell transplant.



Alpha Thalassemia

What is alpha thalassemia?

Thalassemia is an inherited disorder that affects the production of normal hemoglobin (a type of protein in red blood cells that carries oxygen to the tissues of the body). Thalassemia includes a number of different forms of anemia. The severity and type of anemia depends upon the number of genes that are affected.

What causes alpha thalassemia?

Alpha thalassemia is caused by mutations in the alpha chain of the hemoglobin molecule. Normally, there are two alpha chain genes located on each #16 chromosome, for a total of 4. The alpha chain is an important component of fetal hemoglobin (which is usually made before birth) and hemoglobin A and hemoglobin A2 (which are present after birth). How these genes are altered determines the specific type of alpha thalassemia in a child:

• alpha thalassemia major - all four alpha chain genes are deleted, which is so severe that death can occur in utero (prior to birth).  Intrauterine transfusions are often necessary to carry a baby to term, and after birth, these babies are dependent on red blood cell transfusions.  Carrying a baby with this to term also poses a health risk to the mother.
  
• alpha thalassemia carrier - two alpha chain genes are deleted, either:
  
  • both from the same #16 chromosome, called a "cis deletion"
    
  • one from both #16 chromosomes, called a "trans deletion" When parents are carriers of the cis deletion, there is a one in four, or 25 percent, chance with each pregnancy, to have a baby with alpha thal major. Carriers of the cis deletion versus the trans deletion can be distinguished by DNA analysis only. DNA testing is usually done from a blood sample, to look at the alpha chain genes on each #16 chromosome, to determine which are deleted.
    
    
• hemoglobin H disease - three alpha chain genes are deleted. Hemoglobin H disease occurs when a person has only one functioning alpha chain gene, resulting in a hemolytic anemia that can worsen with febrile illness or exposure to certain drugs, chemicals, or infectious agents. Persons with hemoglobin H disease are at increased risk to have a child with alpha thal major, since they carry one #16 chromosome with an alpha chain two gene deletion (cis deletion).
  
• silent alpha thalassemia carrier - one alpha chain gene is deleted (the other three are normal). Blood tests are usually normal and the only way to confirm a silent carrier is by DNA studies.

How is alpha thalassemia diagnosed?

Alpha thalassemia is most commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and the Mediterranean region. Carrier status can be determined by the following:

• complete blood count (CBC) - a measurement of size, number, and maturity of different blood cells in a specific volume of blood.
  
• hemoglobin electrophoresis with A2 and F quantitation - a lab procedure that differentiates the types of hemoglobin present.
  
• FEP (free-erythrocyte protoporphyrin) and ferritin - to exclude iron deficiency anemia.

All of these studies can be performed from a single blood sample. Prenatal diagnosis is determined from CVS (chorionic villus sampling) or amniocentesis.

Treatment for alpha thalassemia:

Specific treatment for alpha thalassemia will be determined by your child's physician based on:

• your child's age, overall health, and medical history
• extent of the disease
• your child's tolerance for specific medications, procedures, or therapies
• expectations for the course of the disease
• your opinion or preference

Treatment for alpha thalassemia may include:

• daily doses of folic acid
• blood transfusions (as needed)
• surgical removal of the spleen (if necessary)



thalassemia major

Thalassemia major occurs when a child inherits two mutated genes, one from each parent. Children born with thalassemia major usually develop the symptoms of severe anemia within the first year of life. They lack the ability to produce normal, adult hemoglobin and experience chronic fatigue. They may also fail to thrive.

Two major consequences of the genetic defect of thalassemia are severe anemia and expansion of the bone marrow in the body’s effort to produce more red blood cells. This leads to poor growth, impaired physical activities, facial and other bone deformities, fragile bones and enlargement of the liver and spleen. If left untreated, it will lead to death within the first decade of life. The only treatment to combat severe anemia is regular blood transfusions and iron chelation therapy.