The Thalassaemia

Thalassaemia is an inherited impairment of hemoglobin production, in which there is partial or complete failure to synthesize a specific type of globing chain. The exact nature of the defect varies and it is probable that a number of different faults occur along the pathway, which translates the genetic information into a polypeptide chain. The gene itself may be deleted; it usually is in alpha-Thalassaemia. When the abnormality is heterozygous, synthesis of hemoglobin is only mildly affected and little disability occurs. Synthesis is grossly impaired when the patient is homozygous and there is an imbalance in polypeptide chain production. The chains produced in excess precipitate in the cell, forming Heinz bodies.

Beta-Thalassaemia

Failure to synthesize beta chains (beta-Thalassaemia) is the most common type and is seen in highest frequency in the Mediterranean area. Heterozygotes have Thalassaemia minor, a condition in which there is usually mild anemia and little or mo clinical disability. Homozygotes (Thalassaemia major) either is enable to synthesize hemoglobin A or at best produce very little and, after the first 4 months of life, develop profound hypo chromic anemia. The diagnostic features are listed in the information box.

Beta-Thalassaemia minor is often detected only when iron therapy for a mild microcytic anemia fails. The diagnostic features are also summarized in the information box. Symptoms are absent or mild. Intermediate grades of severity occur.
Diagnostic Features Of Beta-Thalassaemia 

Major 

Profound hypo chromic anemia

Evidence of severe red cell dysphasia

Erythroblastosis

Absence or gross reduction of the amount of hemoglobin A

Raised levels of hemoglobin F

Evidence that both parents have Thalassaemia minor

Minor 

Mild anemia

Microcytic hypo chromic erythrocytes (not iron-deficient)

Some target cells

Punctate basophilic

Raised resistance of erythrocytes to osmotic lysis

Taised hemoglobin A2 fraction

Evidence that one parent has Thalassaemia minor

Management

The treatment of beta-Thalassaemia major is given in Table 11.11. Cure is now a possibility for selected children, with allergenic bone marrow transplantation

Prevention

It is possible to identify a fetus with homozygous beta-Thalassaemia by obtaining chronic villas material for DNA analysis sufficiently early in pregnancy to allow termination of pregnancy. This examination is appropriate if both parents are known to be carriers (beta-Thalassaemia minor) and will accept termination.

The reduction or absence of albha chain synthesis is common in South-east Asia. There are two alpha gene loci on chromosome 16 and therefore four alpha genes. If one is deleted there is on clinical effect. If two are deleted there 

may be mild hypo chromic anemia. If there are deleted the patient has hemoglobin H disease and if all four are deleted the baby is stillborn (hydrous fetalis). Hemoglobin H is a beta-chain tetramer formed from the excess of chains. It is functionally useless. Treatment of hemoglobin H disease is similar to that of beta-Thalassaemia of intermediate severity. In some patients the disorder is due to a combination of alpha-Thalassaemia genes with genes, which produce a functionally useless globing chain, Hb Constant Spring. The combinations are shown in the information box.

Alpha-Thalassaemia

Cause

• Failure of production of hemoglobin due to gene deletion

Age and sex

• Both sexes from birth onward

Genetics

• 2 alpha chain genes from each parent

Presentation

• Hydrous fetalis: all genes deleted
• Hemoglobin H: three genes deleted
• Mild hypo chromic microcytic anemia: two genes deleted

Treatment

• Hydrous fetalis: none available
• Hemoglobin H: no specific therapy required; avoid iron therapy; folic acid if necessary

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