Thalassemia

A heterogeneous group of inherited disorders of hemoglobin synthesis Characterized by the absence or reduced output of one or more of the globin chains of hemoglobin

Orang tua Pembawa sifat

Orang tua Pembawa sifat

Orang tua Pembawa sifat

Orang tua normal

Pembawa sifat

Thalassemia Normal Major

Pembawa sifat
Seminar Awam, 21-06-2007

Normal

Pembawa sifat

Seminar Awam, 21-06-2007

4 2 2 4 (HbH)

22 4

22 = 97% (HbA)

22 4 (HbBarts) 22 - 4 ?

-Thalassemia

22 (HbF) < 1% 22 (HbA2) = 2,5%

22 (HbF) 22 (HbA2)

Normal

-Thalassemia

2 2 = 97 % (Hb A)

2 2 4

2 2 4 (Hb H)

2 2 (Hb F)< 1 % 2 2 (Hb A2) 2-3 %

- Thal

2 2 4 (Hb Bart`s) 2 2 4 ?

2 2 (Hb F) 2 2 (Hb A2)

Normal

- Thal

22
HbF
Selective survival of HbF-containing cells

Excess

Precipitation Fe free radicals

Haemolysis Splenomegaly (pooling, plasma volume expansion)

Destruction of RBC precursors Ineffective Erythropoiesis

High oxygen affinity of red cells

Tissue hypoxia Erythopoietin

Anaemia

Marrow expansion
Increased iron absorption Iron loading

Transfusion

Bone deformity Increased metabolic rate Wasting Gout Folate deficiency

Endocrine deficiencies Cirrhosis Cardiac failure Death

The pathophysiology of thalassaemia

Modified from Weatherall, DJ Post Graduate Haematology, 1999

Classification of thalassemia
Clinical classification Genetic classification Molecular classification

Clinical classification
Thalassemia major Thalassemia minor Thalassemia intermedia

Genetic classification
thalassemia thalassemia thalassemia thalassemia thalassemia thalassemia HPFH

Molecular classification
/39CT39CT
genotype of homozygotes for a common Mediterranean non sense mutation

/39CTIVS-1,1GA
genotype of compound heterozygotes of another common Mediterranean mutation

The thalassemias
Thalassemia Normal Minor Major genes / +/ o/ +/+ o/o HPFH / Globin chains 2 2 22, 22, 22 2 2, 2 2, 22, 2 2 , 2 2 2 2 Hemoglobin A A, A2, F A, A2, F F, A2 F Anemia None Mild Severe Severe Mild

Diagnosis
Based on: Family history Physical examination Laboratory test: Complete peripheral blood examination Bone marrow expertise Hemoglobin electrophoresis Molecular studies

Management
Transfusion of PRC Iron chelation Switching the gene Bone marrow transplantation Gene therapy

Endocrine Complications:
1. 2. 3. 4. 5. Growth retardation Hypothyroidism Hypoparathyroidism Glucose intolerance and diabetes Delayed puberty and hypogonadism

Weatherall DJ, Post Graduate Haematology, 1999

Prevention
Genetic counseling Antenatal diagnosis, which may lead to termination of conception