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. The loss of one of the two α-globin alleles (-α) on chromosome 16 causes α+-thalassemia, whereas α0-thalassemia is due to inactivation of both α-globin alleles (--). 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.
Reduced or absent α-globin synthesis, mainly caused by deletions of one or both α-globin genes (α1, α2) and less frequently by point mutations, leads to α-thalassemia. The severity of the phenotype depends on the number of affected α-globin genes and the resulting imbalance between α- and β-globin chains. Four intact α-globin genes (αα/αα) are present in the diploid genome of a healthy human. Individuals, who inherit only two or three functional genes, have mild anemia and microcytosis. HbH disease, affecting only subjects with a single active α-globin gene, presents with moderate to severe hemolytic anemia. The most severe manifestation, the loss of all four α-globin genes (--/--), cause homozygous α0-thalassemia (Hb Bart´s hydrops fetalis syndrome), which is generally associated with death in utero.
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 9 alpha-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