THALASSAEMIA

1. THALASSAEMIA KonstantinidouEleni SiligardouMikela-Rafaella

2. THALASSAEMIA The thalassaemias are a group of inherited hematological disorders caused by defects in the synthesis of one or more of the hemoglobin (Hb) chains. β-Thalassaemia is caused by reduced or absent synthesis of ß-globin chains. α-Thalassaemia is caused by reduced or absent synthesis of α-globin chains. Globin-chain imbalances cause hemolysis and impair erythropoiesis. Globally, an estimated 15 million people have thalassaemia

3. Epidemiology • Thalassaemia affects men and women equally and occurs in approximately 4.4 of every 10,000 live births. • α-Thalassaemia is most common in individuals of African and Southeast Asian descent, while • β-thalassaemia is most common in individuals of Mediterranean, African, and Southeast Asian descent. • About 5% of the world's population has a globin variant, but only 1.7% has α- or β-thalassaemia trait. • Thalassaemia trait affects 5-30% of people in these ethnic groups. • 15% of the people in Greece are carriers of “T”.

4. Epidemiology • The prevalence of β-thalassaemia is highest in areas where malaria is (or was) endemic. • Similar to β-thalassaemia, α-thalassaemia is prevalent in tropical and subtropical regions, where malaria was or still is endemic. • It is thought that carriers of hemoglobinopathies have a degree of protection against malaria, although the mechanism underlying this protection is unknown.

5. Inheritance • Scientists think that this disorder is going to have a major effect on the world in the near future. • This disorder may be given to offspring when the parents both have the heterozygous genotype.

6. Pathophysiology Hemoglobin (Hb) consists of an iron-containing heme ring and four globin chains: two α and two non-α. The composition of the four globin chains determines the Hb type. Normal Haemoglobin • HbA - α2β2 Adult HbA • HbA2 - α2δ2 • HbF – α2γ2 Fetal Hb

7. Each goblin chain have separate genetic control α –thalassaemia affect α-chain synthesis β –thalassaemia affect β-chain synthesis

8. β-Thalassaemia • β-Thalassaemia is characterized by the deficient production of the β-globin chains of hemoglobin (Hb). This typically arises due to mutations in the β-globin gene. Over 200 mutations have been identified in this gene, and the type of mutation can influence the severity of the disease.

9. Forms of β-Thalassaemia • The three main forms of β-thalassaemia, in order of decreasing severity, are: • β-thalassaemia major (mutations in both alleles, homozygous) • β-thalassaemiaintermedia (diverse mutations) • β-thalassaemia minor (single mutation, heterozygous)

10. Forms of β-Thalassaemia – Order of severity HSCT = hematopoietic stem cell transplantation

11. Thalassaemia Trait • Individuals with thalassaemia trait do not require treatment or long-term monitoring. They usually do not have iron deficiency, so iron supplements will not improve their anemia. Iron therapy should only be administered if iron deficiency occurs. • Individuals with thalassaemia trait have a normal life expectancy. • Most individuals with thalassaemia trait are diagnosed when their complete blood count shows a mild microcytic anemia. • β-Thalassaemia trait is asymptomatic and is associated with microcytosis, usually no or mild anemia, no splenomegaly, and no bone disease

12. α-Thalassaemia An absence or deficiency of α-chain synthesis due to delation of α-genes.

13. Types of Thalassaemia: α-Thalassaemia α-Thalassaemia is characterized by the deficient production of the α-globin chains of hemoglobin (Hb). This typically arises due to mutations in the α-globin gene. Forms of α-Thalassaemia α-Thalassaemia is one of the most common hemoglobin genetic abnormalities. It can be divided into four clinical conditions of increasing severity. There are: • two carrier states, silent and trait, and • two clinically relevant forms, α-thalassaemia or HbH disease and Hb Bart's hydropsfetalis syndrome.

14. Clinical classification of а-thalassaemia

15. Thalassaemia: Clinical Consequences • Anemia • Splenomegaly • Impaired growth and development • Endocrine disorders (e.g. hypogonadism, type 2 diabetes) • Venous and arterial thromboembolic events • Osteopenia • Osteoporosis

16. Laboratory Diagnosis of Thalassaemia

17. Thalassaemia: Diagnosis Diagnostic methods for β-thalassaemia major include: • Genetic studies and prenatal diagnosis • Clinical history and physical examination • Complete blood count (CBC) • Blood films • Hb electrophoresis • Imaging studies • Differential diagnosis

18. Treatment of Thalassaemia Potentially Curative Treatment • The only potentially curative treatment option for patients with β-thalassaemia major is hematopoietic stem cell transplantation (HSCT). Therapy consists primarily of supportive therapy based on clinical manifestations.

19. Potentially Curative Treatment

20. References • http://www.ironhealthalliance.com • Pathogenesis and Lab Diagnosis Presentation at Seminar on observation of World Thalassaemia Day 2009 Presentation: 10 May 2009, Dinajpur Medical College • http://marshallteachers.sandi.net Thank you!