What is beta thalassemia?

Beta thalassemias are a group of blood disorders hereditary . They are forms of thalassemia is caused by reduced or no synthesis of beta-chain of hemoglobin leads to different results, from anemia heavy to individuals without clinical symptoms. Beta thalassemia is a blood disorder that reduces hemoglobin production . Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body . The global incidence rate is estimated to be one in 100,000. Beta thalassemias is caused by the above HBB gene mutation chromosome , No. 11 is inherited in the type of spontaneous diving. The severity of the disease depends on the nature of the mutation.  

In people with B eta thalassemia , low hemoglobin levels lead to lack of oxygen in many parts of the body. Affected people also have a lack of red blood cells ( anemia ), which can cause pale skin, weakness, fatigue and more serious complications. People with B eta thalassemia are at risk of developing an abnormal blood clot.       

Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia Major (also known as Cooley anemia) and thalassemia intermediates. Of the two, thalassemia Major is heavier.   

Signs and symptoms of large beta thalassemia appear within the first 2 years of life. Children with life-threatening anemia. They do not gain weight and grow at the expected rate (do not thrive) and may develop jaundice and iris (yellow skin). Affected people may have enlarged spleen, liver and heart, and their bones may be deformed. Some adolescents with primary thalassemia experience delayed puberty. Many people with thalassemia have symptoms so severe that they need regular blood transfusions to replenish their supply of red blood cells. Over time, the blood transfusion can lead to chronic accumulation of iron in the body, leading to liver problems, heart and hormones.      

Intermediate thalassemia is milder than thalassemia Major. Signs and symptoms of thalassemia-mediated disease appear in young children or later in life. People affected are mild to moderate anemia and may also have slow growth and bone abnormalities.  

Beta thalassemia is a fairly common blood disorder worldwide. Thousands of babies with beta thalassemia are born each year. Beta thalassemia occurs most often in people from Mediterranean countries, North Africa, the Middle East, India, Central Asia and Southeast Asia.      


Mutations in the HBB gene cause beta thalassemia . The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is an ingredient (subunit) of hemoglobin . Hemoglobin consists of four protein subunits, typically two beta-globin subunits and two subunits of another protein called alpha-globin.           

Some mutations in the HBB gene prevent the production of any beta-globin. The absence of beta-globin is called beta-zero (B ) thalassemia. The gene mutations HBB other allows the creation of beta-globin, but some numbers fell. A reduced amount of beta-globin is called thalassemia beta-plus (B ). However, having B or B thalassemia does not necessarily predict the severity of the disease; People with both types have been diagnosed with thalassemia major and thalassemia intermediates.        

The lack of beta-globin leads to a decrease in the amount of functional hemoglobin. Without enough hemoglobin, red blood cells do not grow normally, causing a shortage of mature red blood cells. A low number of mature red blood cells leads to anemia and other related health problems in people with beta thalassemia .     

 What are the signs and symptoms of Beta Thalassemia?

People with beta thalassemia trait usually do not have any symptoms.

Children with intermediate or primary B eta thalassemia may not exhibit any symptoms at birth, but usually develop them during the first 2 years of life. They may have symptoms of anemia, such as: 

  • tired
  • shortness of breath
  • fast heart beat
  • pale skin
  • yellow skin and eyes (jaundice)
  • cheerless
  • slow growth

People with large or intermediate beta thalassemia often have an accumulation of iron in their bodies, either from the disease itself or from repeated blood transfusions. Excess iron can damage the heart , liver and endocrine system .       

People with B eta thalassemia Major may have other serious health problems, including:

  • bone deformities and broken bones from changes in the bone marrow (where red blood cells are made)
  • a spleen extended for bodies active than normal. Doctors may need to remove the spleen if it is too large.    
  • infection, especially if the doctor removes the spleen (the spleen helps fight some infections)


Proposed results

Should suspected beta-thalassemia in newborns or children younger than two years old with the results of the screening clinical or neonatal following :       

  • Clinical results
    • Severe microscopic anemia
    • Mild jaundice
    • Enlarged liver

Note: If untreated, children affected usually manifests not thrive and expand the bone marrow to compensate for ineffective erythropoiesis.   

  • Newborn screening results. A positive or suggestive result is done through newborn screening (for example, through capillary electrophoresis, isoelectric focus or high-performance liquid chromatography on newborn blood spots)    

Thalassemia should be suspected in people who appear at a later age with similar but milder clinical findings. Individuals with thalassemia intermedia do not need regular blood transfusion treatment.  

Minor thalassemia usually has no clinical symptoms, but sometimes mild anemia. 

Diagnostic settings

Diagnosis-thalassemia was established at a proband greater than 12 months old based on the hematological test results of hypocromic anemia ( Table 1 ), anisopoikilocytosis analysis with red blood cells with cell nuclei on cells peripheral blood has no hemoglobin A and an increase in hemoglobin F ( Table 2 ).          

Diagnosis-thalassemia was established in a proband younger than 12 months old based on the following findings:    

  • Positive or suggestive newborn screening results  
    • The diagnosis of β -thalassemia (in which no beta-globin protein is made) can be made at birth by detecting complete absence of hemoglobin A.  
    • The definitive diagnosis of β -thalassemia (in which beta-globin protein is produced but at a reduced level) by these techniques is not possible in infancy because the amount of hemoglobin A decreases gradually overlapping the range for infants. normal birth.  
  • Micro pigmented anemia with ischemic disease and red blood cells with nuclei on peripheral blood smear
  • Parallel pathogenic variants in HBB were identified in molecular genetic assays (see Table 3 ).      

Hematological results

RBC indices indicate micro ischemia ( Table 1 ).   

Table 1. RBC index in Beta-Thalassemia

Peripheral blood smear

  • Affected individuals demonstrate the morphological changes of red blood cells (RBC) of microcytosis, hypochromia, anisocytosis, poikilocytosis (tear and prolonged cell) and nuclear red blood cells. The number of erythrocytes is related to the degree of anemia and increases markedly after splenectomy. 
  • The carrier exhibits moderate volume reduction (MCV), moderate hemoglobin (MCH) ( Table 1 ) and less severe RBC morphological changes in the affected people . Erythroblasts are often not seen.     

Qualitative and quantitative analysis of hemoglobin (by cellulose acetate electrophoresis and DE-52 microchromatography or HPLC) determines the amount and type of hemoglobin present. The following types of hemoglobin (Hb) are most relevant to -thalassemia:  

  • Hemoglobin A (HbA): two alpha globin chains and two beta globin chains (α β )    
  • Hemoglobin F (HBF): two chains of alpha globin and two chains of gamma globin (α γ )    
  • Hemoglobin A (HbA ): two chains of alpha globin and two plain globin chains (α δ )        

Samples of hemoglobin in-thalassemia vary according to type-thalassemia ( Table 2 ).  

 Table 2. Hemoglobin samples in Beta-Thalassemia (Age> 12 months)

Hemoglobin and HPLC electrodes also detect other types of hemoglobin (S, C, E, O Arab , Lepore) that can interact with-thalassemia.  

Molecular genetic testing

Methods of genetic testing molecules are proposed for beta-thalassemia is testing single gene :       

  • Sequence analysis of HBB is performed first, followed by analysis of deletion / replication target gene if only find one or no variant disease .          

Note: Analysis HBB is complicated by the presence of members of the family genetic high similarity as well as a pseudogene , HBBP1 ; Therefore, any test that tests the HBB sequence must be confirmed to ensure specificity of the active gene.              

  • In at-risk populations, targeted analyzes for pathogenic variants may be performed first based on ancestors because common pathogenic variants are restricted to each at-risk population.  

Table 3. Molecular genetic testing is used in Beta-Thalassemia

Monitoring and treatment

Evaluation after initial diagnosis

To establish disease severity and need in an individual diagnosed with thalassemia, the following assessments are recommended if they have not been completed:

  • The first step after diagnosis of thalassemia in an individual is to distinguish between those with thalassemia-mediated disease (needing continuous blood transfusion on an as-needed basis) from those with primary thalassemia (need a regular blood transfusion program piercing). 

The following should be included in investigations when deciding who will receive a blood transfusion:

  • Amnesty c receive diagnosis thalassemia
  • Hemoglobin level <7 g / dL twice, more than two weeks apart (not including all other causes of infection, such as infection), or the presence of the following features, regardless of hemoglobin level:
    • Change face
    • Poor growth
    • Fracture
    • Hematopoietic has clinical significance
  • Advice with a clinical geneticist and / or genetic counselor is appropriate.

Treatment of manifestation

Large thalassemia. Regular blood transfusion helps treat anemia, inhibits erythropoiesis and inhibits increased absorption of iron from the gastrointestinal tract. 

  • Before starting a blood transfusion, the following is absolutely necessary:
    • Get vaccinated for hepatitis B
    • Extensive erythrocyte antigen tests , including Rh, Kell, Kidd, and Duffy and determination of serum immunoglobulin – a method that then detects people with IgA deficiency, who need special blood unit preparation (washing) several times) before each blood transfusion
  • The blood transfusion regimen designed to achieve Hb before blood transfusion is 95-100 g / L.
  • Blood transfusions are usually given every two to three weeks.

Intermediate thalassemia disease. Treatment for people with thalassemia-mediated disease is symptomatic and is based on splenectomy and folic acid supplementation. 

  • Treatment of extracurricular erythrocytes is based on radiation therapy, blood transfusion, or in selected cases, hydroxyurea (with a protocol similar to that used for sickle cell disease ).  

Hydroxyurea also increases the gamma globin chain and may have other indeterminate effects.

  • People with thalassemia-mediated disease may be overloaded with iron due to increased absorption of iron from the digestive tract or by frequent blood transfusions; Treatment of chelation with deferasirox has been shown to be safe and effective in people 10 years of age and older with serum iron concentrations of ≥5 mg Fe / g or serum ferritin 800 ng / mL (thereafter threshold risk Severe iron – the incidence of related illness is increased) . 

Marrow transplant

  • A bone marrow transplant (BMT) from a healthy person identical to HLA represents an alternative to traditional blood transfusion and chelation therapy. If successful BMT, the process t h Pass the iron can be reduced down . 
  • BMT results relate to pre-transplant clinical conditions, especially the presence of the liver, degree of fibrosis and iron accumulation. In children who lack these risk factors, the disease-free survival rate is higher than 90%. Adults with beta-thalassemia have an increased risk of transplant-related toxicity due to the advanced stage of the disease and a two-year survival rate of 80% and a two-year survival rate of 76% with a treatment regimen . current value.  
  • Affected individuals without appropriate donors can also benefit from mother-to-child transplants .

Umbilical cord blood transplant. Umbilical cord blood transplant from a related donor provides a successful cure and is associated with a low risk of GVHD. For couples who have had a child with thalassemia and performed a prenatal diagnosis in the next pregnancy, the prenatal determination of HLA compatibility between the affected child and the unborn baby is unaffected. allows placental blood to be taken at birth and the choice of affected umbilical cord blood transplant. In addition, in the event that the fetus is affected and the child is not previously affected, the couple may decide to continue pregnancy and pursue BMT afterwards, using the unaffected child as a donor. .        

Preventing the first manifestation

Early detection of anemia, the main manifestation of the disease, allows early treatment and monitoring.

Prevention of secondary complications

Iron overload transmission

The most common secondary complications are those associated with transfusion iron overload, which can be prevented by adequate chelation.

Evaluation of iron overload

  • Serum ferritin concentration. In clinical practice, the effectiveness of chelation agents is monitored by regular determination of serum ferritin levels. However, serum ferritin levels are not always reliable for assessing the burden of iron because it is influenced by other factors, most importantly the extent of liver damage. 
  • Liver biopsy Determination of liver iron concentration in liver biopsy samples shows a high correlation with the total iron accumulation in the body and is the gold standard for assessing the liver’s iron overload. However, liver biopsy is an invasive technique involving the ability (albeit low) of complications; The iron content of the liver can be affected by cirrhosis, which often occurs in people with iron overload and hepatitis C virus infection; and uneven distribution of iron in the liver can lead to false negative results.     
  • Magnetic biometrics (SQUID), which reliably measures liver iron levels, is another option; however, magnetic sensitivity measurement is currently only available in a limited number of centers worldwide.  

Heart disease

Particular attention is paid to the early diagnosis and treatment of heart disease because of its important role in determining the prognosis of people with thalassemia. Evaluation of cardiomyopathy with MRI and monitoring of cardiac function combined with increased chelation may lead to long-term prognosis. 


Osteoporosis is a common complication in adults with thalassemia major or intermediate thalassemia. Its origin is multifactorial , making it difficult to manage. Treatment includes appropriate hormone replacement, effective blood transfusion and chelation, vitamin D use and regular physical activity. There is sufficient evidence to support the use of bisphosphonates in the management of thalassemia-related osteoporosis (to prevent bone loss and improve bone mineral density).      


For people with thalassemia major, to monitor the effectiveness of blood transfusion and chelation therapy and their side effects include:

  • Monthly health examination by a physician familiar with the affected individual and the disease   
  • Every three months: evaluate liver function tests (serum ALT levels), determine serum ferritin levels and assess growth and development (in early childhood)
  • Annual
    • Eye exam and audiology
    • Complete cardiac assessment, and evaluation of thyroid, endocrine pancreas, parathyroid gland, adrenal gland and pituitary function
    • Evaluate liver ultrasound and determine serum alpha-fetoprotein level in adults with hepatitis C and iron overload for early detection of HCC
    • Measure bone density to assess osteoporosis in adults
    • MRI of the liver and heart muscle
  • Regular gallbladder ultrasound for early detection of gallbladder stones, especially in people with Gilbert’s syndrome genotype (i.e., the presence of the module (TA) / (TA) in the stimulant UGT1A )           
  • In patients taking deferasirox: monitoring serum creatinine concentration, creatinine clearance and / or plasma cystatin C before treatment, weekly for the first month after initiation or adjustment of therapy, and monthly after that. Liver function tests should be performed before starting treatment, every two weeks for the first month and monthly thereafter in these patients. 
  • Monitor the patient’s neutrophil count per week and in case of infection in patients taking deferiprone

Circumstances to avoid

The following should be avoided:

  • Alcohol consumption, in people with liver disease has a synergistic effect with iron-induced liver damage
  • Iron preparations

Assess relatives at risk

Early detection of anemia, the main manifestation of -thalassemia, allows timely and appropriate treatment and monitoring.

Assessments may include:

  • Molecular genetic testing if known family disease variants
  • Hematological test if the family pathogenic variants are not known .








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