Molecular analysis of beta-globin involves screening for the 22 most frequent hemoglobin beta chain mutations in Mediterranean populations.
Beta thalassemia is caused by reduced (β+) or zero (β0) synthesis of the hemoglobin tetrameric beta chains. Three clinical and hematological conditions of increasing severity have been identified, namely the carrier status of beta-thalassemia (stigma), intermediate thalassemia, and major thalassemia (or Mediterranean anemia). The carrier status of beta-thalassemia, which results from heterozygotic status for beta-thalassemia, is clinically asymptomatic and is defined by specific hematological characteristics. Major Mediterranean anemia is severe transfusion-dependent anemia. Intermediate thalassemia is a clinically and genetically very heterogeneous group of thalassaemias, comprising disorders ranging in severity from asymptomatic carrier to severe transfusion-dependent anemia.
The clinical severity of beta-thalassemia is related to the extent of the imbalance between the alpha and non-alpha globin chains. The beta-globin (HBB) gene is located on the short arm of chromosome 11, in a region that also contains the delta globin gene, the fetal epsilon globin gene, the fetal A-gamma, and G-gamma genes as well as the pseudogene (ψB1). Beta thalassaemias are a very heterogeneous group at the molecular level. To date, more than 200 mutations causing the disease have been identified. The majority of mutations are simple nucleotide substitutions, deletions, or oligonucleotide insertions that lead to the displacement of the reading frame. Rarely, beta-thalassemia results from deleting a large portion of the gene. In addition to different phenotypes as a result of the heterogeneity of the beta-globin gene locus, the beta-thalassemia phenotype can also be modified by the action of genetic factors that are outside the globin gene cluster and do not affect embryonic hemoglobin. Among these factors are those that affect bilirubin, iron, and bone metabolism.
Due to the high prevalence rate of HBB mutations in specific populations (such as Greek) and the availability of genetic counseling and prenatal diagnosis, screening allows at-risk couples to make informed choices about their reproductive choices.
The clinical management of major thalassemia consists of regular red blood cell transfusions and chelation therapy to remove excess iron.
Laboratory test results are the most important parameter for the diagnosis and monitoring of all pathological conditions. 70%-80% of diagnostic decisions are based on laboratory tests. The correct interpretation of laboratory results allows a doctor to distinguish "healthy" from "diseased".
Laboratory test results should not be interpreted from the numerical result of a single analysis. Test results should be interpreted in relation to each individual case and family history, clinical findings, and the results of other laboratory tests and information. Your personal physician should explain the importance of your test results.
At Diagnostiki Athinon we answer any questions you may have about the test you perform in our laboratory and we contact your doctor to get the best possible medical care.