Summary of Thalassaemia

Thalassaemia Summary

Main types – alpha thalassaemia
- severe types- Hb Barts (all alpha haemoglobin genes abnormal/missing)
- Hb H disease (3 missing alpha haemoglobin genes, mild persistent anaemia)

- beta thalassaemia
- severe types – beta thalassaemia major ( 2 beta thalassaemia genes, most haemoglobin does not work)
- beta thalassaemia intermedia (2 beta thalasaemia genes, some haemoglobin works)
- Thalassaemia minor

Epidemiology

-carried by 150 million or 3% of world population
-Beta thalassaemia more common in Mediterranean countries

In Malaysia, mostly among Malays and Chinese. Only small percentage of Indians
-Carrier for B.Thalassaemia is 3 to 5%
-In 1995, 8000 affected with HbE beta Thalassaemia, 8000 affected with homozygous beta Thalassaemia.
-2140 in Malays
-2240 in Chinese

For alpha thalassaemia, 15.8% of pregnant women in 2005 are carriers.

Predisposing Factors
Factors that increase risk
-family history
-ancestry

Inheritance
Alpha thalassaemia
-4 genes needed to make alpha globin protein chain
-if one or more gene missing, alpha thalassaemia trait

Beta Thalassaemia
-2 genes needed to make beta globin protein chain
-one or both altered, beta thalassaemia


Pathogenesis and genetics
Alpha thalassaemia
-silent carrier state(one gene deletion)
-loss of two genes
-imbalance causes accumulation of beta chains. Beta chains begin to associate in groups of four producing abnormal haemoglobin(hemoglobin H)
-hydrops fetalis-hemoglobin barts

Beta Thalassaemia
-one gene affected, one normal. Degree of imbalance depend on residual production capacity of defective beta globin gene.
-two gene affected.

Thalassemia minor
-small red cells and mild anaemia

Thalassaemia intermedia
-significant anaemia
-able to survive without blood transfusion
-Hb of below 7 or 8 gm/dl

Thalassaemia major
-severe anaemia
-can survive but terrible deformities
-blood transfusion causes iron overload

Signs and Symptoms
Alpha thalassaemia silent carriers
-no symptoms

Alpha of Beta Thalassaemia trait
-mild anemia

Beta Thalassaemia Intermedia
-mild to moderate anemia
-slowed growth
-bone problems
-enlarged spleen

Beta Thalassaemia major
· Pale appearance
· Poor appetite
· Dark urine
· Slowed growth and delayed puberty
· Jaundice(a yellowish color of the skin or whites of the eyes)
· Enlarged spleen ,liver, heart
· Bone deformities (especially bones in the face)
· Pallor
· Fatigue
· Tiredness
· Weakness
· Shortness of breath
· Blood in urine
· Skull deformity
· Skeleton deformity
· Thickening skull
· Thickening facial bone
· lack of beta globin causes a life-threatening anemia
· Therefore requires regular blood transfusions
· Life long transfusions lead to iron overload
· Must be treated with chelation therapy to prevent early death from organ failure.
Haemoglobin H disease
— Severe anemia
— Fatigue
— Pale appearance
— Poor appetite
— Dark urine
— Slowed growth and delayed puberty
— Jaundice(a yellowish color of the skin or whites of the eyes)
— Enlarged spleen
— Bone deformities (especially bones in the face)

E Beta Thalassaemia
-similar to Beta Thalassaemia but may be severe to Beta Thalassaemia Major

Complications
-Iron Overload
-Infections
-Bone deformities
-Splenomegaly
-Anaemia
-Still Birth

Screening and Diagnosis
-Complete Blood Count
-Haemoglobin electrophoresis
-Family genetic study
-Antenatal test
-Genetic studies
-Iron test
-Modified osmotic fragilty test
-Modified dichlorophenolindophenol test
Treatment and Management
-Gene Therapy
-Genetic Counselling
-Chelation Therapy
-Blood Transfusion

Ethical/Legal Issues for Savior Baby
-Read Majids thing. Its quite summarized already. =)