Beta-thalassemia intermedia and Beta-thalassemia major - HBB gene
Thalassemia is an alteration of hemoglobin, characterized by genetic alterations that cause the absence or reduction of the expression of α or β globin chains, resulting in alpha or beta thalassemia, respectively. It is one of the most frequent genetic abnormalities in humans, especially in the Mediterranean countries, South East Asia and localized areas in Africa and India. In people with β-thalassemia, low hemoglobin levels lead to oxygen deficiency in many parts of the body. Affected individuals also have anemia, which manifests with pale skin, weakness, tiredness, and more serious complications. People with β-thalassemia have an increased risk of developing abnormal blood clots.
β-thalassemia is classified into two types depending on the severity of symptoms: β-thalassemia major, also known as Cooley´s anemia, and β-thalassemia intermedia. Of the two types, thalassemia major is the most severe. The signs and symptoms of β-thalassemia major appear during the first 2 years of life. Affected children have severe anemia, stunted growth, and jaundice. In addition, these individuals may have an enlarged spleen, liver, and heart, as well as bone deformities. β-thalassemia intermedia is milder and signs and symptoms generally appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may have abnormal bone growth.
Beta-thalassemias (β-thalassemias) are generated by point mutations in the HBB gene, located on the short arm of chromosome 11 (11p15.5). This gene codes for the β-globin subunit of hemoglobin. Hemoglobin is a tetrameric protein responsible for the transport of oxygen to the cells and tissues of the body, made up of four subunits: two α-globin subunits and two β-globin subunits (α2, β2). Each of these subunits can transport a heme group necessary for the transport of oxygen to the lungs, since each group is a carrier of an oxygen molecule. As a consequence, the lack of β-globin generates a reduced amount of functional hemoglobin and without it, red blood cells cannot develop normally and affected individuals will develop anemia and other health problems.
About 400 mutations in the HBB gene have been identified in people with β-thalassemia. Most mutations involve a nucleotide change at or near the HBB gene. Other mutations insert or delete a small number of nucleotides in the HBB gene. Some mutations in the HBB gene cause the absence of β-globin chains (β0 thalassemia). Others cause a reduction in expression (β+ thalassemia). Both individuals with β0 thalassemia and β+ thalassemia have been diagnosed with thalassemia intermedia and thalassemia major. People with β-thalassemia major usually require medical attention before they are two years old and require regular red blood cell transfusions to ensure their survival. β-thalassemia intermedia, however, does not require regular transfusions and is usually diagnosed later.
β-thalassemia is inherited in an autosomal recessive pattern, meaning that both copies of the HBB gene in each cell must have the mutations for the alteration to be expressed. The parents of an individual with autosomal recessive disease have a copy of the mutated gene, but they generally do not show signs and symptoms of the disease. Sometimes people with a single HBB gene mutation in each cell develop mild anemia. These mildly affected people are said to have β-thalassemia minor. In a small percentage of families, the HBB gene mutation is inherited in an autosomal dominant manner. In these cases, one copy of the altered gene in each cell is sufficient to express the signs and symptoms of β-thalassemia.
Tests carried out in IVAMI: in IVAMI we carry out the detection of mutations associated with β-thalassemia, by means of the complete amplification by PCR of the exons of the HBB gene, and their subsequent sequencing.
Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample). In case of prenatal diagnosis, amniotic fluid or chorionic villi.