β-Thalessemia
Hemoglobin is a tetramer which is composed out of 2 α-chains and 2 non α-chains. In the normal synthesis, α-chains and non α-chains (β-chain, γ-chain and δ-chain) are synthesized with no overproduction or underproduction. Thalassemias are hereditary disorders that are caused by abnormally synthesized globin chains.
In thalassemic disorders, due to a quantitative defect in synthesis of a specific chain, free α chains or single globin chains such as HbH(β4), HbBart’s(γ4) of hemoglobin could be synthesized. β-Thalassemia in an analogous manner means reduced or missing production of hemoglobin β-chains, which is compensated by overproduction of γ-chains and δ-chains. Consequently, hemoglobin A2 (α2δ2) and hemoglobin F(α2γ2) are often elevated in β-Thalassemia. The Tosoh G8 & G11 HPLC can separate HbF and HbA2 quickly and accurately. HbF and HbA2 are reported in a percentage of the total amount of hemoglobin present in a sample within 6.0 min.
The β-thalassemias are a group of conditions resulting from a reduced rate of synthesis of the β globin chain. More than 200 b gene mutations have been identified, occurring in a wide range of ethnic groups, and within each geographic population there are unique mutations.
β-thalassemia mutations are divided into two broad categories, β0 (β-zero) thalassemia and β+ (β-plus) thalassemia. In β0 thalassemia there is either an abnormal gene that is not expressed or, less often, gene deletion. In β+ thalassemia there is reduced, but not absent, expression of the abnormal gene so that even in the homozygous state there is still some hemoglobin A production.
β-thalassemia can be divided into three general categories:
- β-thalassemia trait: This state is characterised by heterozygosity of one deleted or mutated gene and one normal functioning gene, and may therefore also be referred to as β thalassemia minor. Individuals with this trait are usually completely asymptomatic.
- β-thalassemia intermedia: This state refers to a clinical phenotype with diverse genetic explanations. These individuals will have a homozygous or heterozygous β globin mutation that causes a decrease in β chain production, but not to the degree that chronic transfusion therapy is necessary. In comparison with a typical patient with β-thalassemia trait, there are significant clinical problems.
- β-thalassemia major or Cooley’s anemia: β-thalassemia major refers to patients with homozygosity or compound heterozygosity for β-thalassemia who are dependent on blood transfusions to maintain life beyond early childhood.
Diagnosing thalassemia traits and diseases
Thalassemia may be suspected if an individual shows signs that are suggestive of the disease. However, in all cases, laboratory diagnosis is essential to confirm the exact diagnosis and to allow for the provision of exact genetic counselling about recurrence risks and testing options for parents and affected individuals. Likewise, screening is recommended to determine trait status for individuals of high risk ethnic groups.
- The following tests are used to screen and diagnose thalassemia disease and/or trait:
Full Blood Count (FBC) - High Performance Liquid Chromatography (HPLC) for quantification of hemoglobin A2 and F
- Free erythrocyte-protoporphyrin (or ferritin or other studies of serum iron levels)
References
Adrain Stephens; Haemoglobinopathies; The Biomedical Scientist; 2004, July, 1-4
Anita J. Catlin; Thalassemia: The facts and the controversies; Pediatric Nursing, November-December 2003, 29 (6), 447-451
Barbara J. Bain; Haemoglobinopathy Diagnosis; 2001 Blackwell Science Ltd.
Nancy F. Olivieri; The β-thalassemias; The New England Journal of Medicine, 1999, July 8, 341 (2), 99-109
P.C.Giordano, M.Herruer, W.Huisman, J.G.J.Pouwels, J.Smit, N.Verhoef, P.Wijermans; Rapport van de werkgroep hemoglobinopathieën van de vereniging hematologische laboratoriumonderzoek. Enquêteresultaten en aanbevelingen t.b.v. dragerschapdiagnostiek en preventie van de hemobglobinopathieën. Uitgegeven door de leden van het landelijk werkgroep hemoglobinopathieën van de vereniging van hematologische laboratoria.
A lot of the above information was obtained from the following websites:
www.hbpinfo.com/en/
www.thalassemia.org/