Thalassemias are severe forms of anemia and a major public health problem. For the large majority of affected individuals there is only supportive management but no ultimate cure, and the focus is on prevention programs based on heterozygous carrier screening and prenatal diagnosis.
In healthy adults 97-98% of total hemoglobin (Hb) is HbA, consisting of two α-globin and two β-globin polypeptides (α2β2). Abnormalities in the structure and synthesis of both globin chains lead to an imbalance causing the two main types of thalassemia: α-thalassemia and β-thalassemia. Two groups of β-globin mutations are distinguished, depending on whether they lead to a reduction (β+) or an absence (β0) of β-globin synthesis. In many regions, α- and β-thalassemia coexist with a variety of different structural Hb variants. These complex interactions give rise to an extremely wide spectrum of clinical phenotypes. Furthermore, an inherited increase of γ-globin expression in patients can partially compensate for the lack of normal β-globin chain synthesis in β-thalassemia as well as sickle cell disease and thereby can ameliorate the clinical phenotype of both disorders.
Numerous defects in the β-globin gene have been identified, many of which cause structural abnormalities, such as HbS (sickle cell hemoglobin), HbC, HBE, or lead to impaired β-globin synthesis, known as β-thalassemia. The clinical manifestations of the disease show a tremendous diversity, which correlates with the underlying genetic defects. β-thalassemia major, the most severe and transfusion-dependent state is characterized by the complete absence of HbA and results from the inheritance of two β0 alleles. Individuals who have inherited a single β-thalassemia allele, whether β0 or β+, have β-thalassemia minor. They are often clinically asymptomatic but may have mild anemia with characteristic hypochromic microcytic red blood cells and elevated levels of HbA2 (α2δ2). The diverse phenotypes ranging between β-thalassemia major and β-thalassemia minor constitute the clinical syndrome of β-thalassemia intermedia, which in most cases results from the inheritance of β+/β+ or β+/β0 alleles.
Genetic counselling of thalassemia patients and their families is offered at CMG.
Prenatal diagnosis requires the most precise molecular diagnosis possible in the index case and is performed at CMG if mutations are detected and confirmed.
Detection: We offer DNA test for the detection of 23 beta-globin gene mutations which are most frequent for our region using the multiplex PCR-amplification followed by reverse-hybridization technique.
Specimen Requirements: genomic DNA is isolated from the peripheral blood, collected in 2 ml EDTA Vacutainer tube (lavender top). In case if DNA is already extracted, the minimum concentration should be 25 ng/µl.
Transportation: The blood specimen can be stored in the refrigerator (for 1 or 2 days) and shipped to CMG at room temperature. In case of the DNA, it can be shipped to CMG at room temperature within 1-2 days.
Turnaround time: 10-15 days
For further information please contact:
Tel.: (+374 10) 544367
Fax: (+374 10) 544366