THALASSAEMIA

Konstantinidou EleniSiligardou Mikela-Rafaella

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

• 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”.

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.

Epidemiology

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.

PathophysiologyHemoglobin (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

Each goblin chain have separate genetic control

α –thalassaemia affect α-chain synthesis

β –thalassaemia affect β -chain synthesis

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.

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-thalassaemia intermedia (diverse

mutations)– β-thalassaemia minor (single mutation,

heterozygous)

Forms of β-Thalassaemia – Order of severity

HSCT = hematopoietic stem cell transplantation

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

α-Thalassaemia

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

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-Thalassaemiaα-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 hydrops fetalis syndrome.

Clinical classification of а-thalassaemia

Condition Clinical characteristics

Silent carrier Clinically and haematologically normal

Thalassaemia trait Microcytosis, hypochromia, and mild anemia

HbH disease Moderate to severe microcytic, hypochromic, haemolytic anemia, mild jaundice, moderate hepatosplenomegaly

Hb Bart's hydrops fetalis syndrome

Severe anemia, generalized edema, ascites, marked hepatosplenomegaly, skeletal and cardiovascular malformations, usually death in utero

Thalassaemia: Clinical Consequences

• Anemia• Splenomegaly• Impaired growth and

development• Endocrine disorders (e.g.

hypogonadism, type 2 diabetes)

• Venous and arterial thromboembolic events

• Osteopenia• Osteoporosis

Laboratory Diagnosis of Thalassaemia

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

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.

Potentially Curative Treatment

Potentially curative Other care options

•Hematopoietic stem cell transplantation (HSCT)

•Blood transfusions•Splenectomy•Hormone replacement therapy•Iron chelation•Treatment of infections and complications

References

• http://www.ironhealthalliance.com

• Pathogenesis and Lab DiagnosisPresentation at Seminar on observation of World Thalassaemia Day 2009

Presentation: 10 May 2009, Dinajpur Medical College

• http://marshallteachers.sandi.net

Thank you!