Antenatal diagnosis of haemoglobinopathies

There are as many as 2,500 genetic defects known to occur in human beings. Some of them (e.g. phenylketonuria and haemophilia) have been cured but most of them are not understood. If a pregnant woman bears a child with a genetic defect, often she is advised to abort it but not to give birth to genetically defected child. Thus, the technique of diagnosis and thereby suggestion for abortion of a genetically defected child is known as antenatal diagnosis. The genetically determined defects of function or synthesis of human haemoglobin is known as haemoglobinopathies.

The inherited haemoglobinopathies are:

1. The structural variants where till now 300 amino acid variants are identified, and
2. The thalassaemias, a condition characterized by reduced or absent synthesis of α and β-globin chain, α and β-thalassaemia respectively.

Methods of antenatal diagnosis:

Antenatal diagnosis is done by taking a few milliliters of amniotic fluid from the foetus of about 16-18 weeks pregnant woman. Foetal blood samples are analyzed by testing for the ability to synthesize globin chains (alpha and beta). Difficulties with the antenatal diagnosis are that the foetus of less than 3 months of age synthesize very little α or β- globin chains. At this stage the foetal blood contains normal level of α and low level of β-chain. Synthesis of β-chain takes place in low amount in foetus of 8 weeks age, and therefore, it is possible to analyze the globin in a foetus but difficult to analyse β-chains (Little, 1981).

The foetus fluid also contains foetally derived fibroblasts which serve, with or without additional culture, as a source of tissue for preparation of foetal DNA. Structural analysis of DNA is done by (a) isolation of all the globin genes as recombinant DNA molecules, and cloning in bacteria, or (b) without cloning the recombinant DNA in bacteria by “Southern Blotting Techniques” (Southern, 1975), and (c) linked polymorphism. A detailed account of DNA analysis of structural genes is given by Little (1981). There are about 35 diseases which have been identified by antenatal diagnosis. This method helps in suggesting the abortion of defected baby, and if possible, to cure. It can be recommended for gene therapy as well. Thus, the antenatal diagnosis is applied for both genetic counseling and gene therapy.

Genetic counseling:

Genetic counseling is a technique which carried out in detail based on antenatal diagnosis and suggested for the possibilities of future progeny. A genetic disease is first identified by a genetic counselor who understands the family history of genetic disease, and then suggests for the possibilities of giving birth to the child or aborting the child. The child may be normal, genetically defected or carrier of genetic disease. Take the case of thalassaemia. Alpha thalassaemia is caused by the presence of two chromosomes each of them carries one dysfunctional globin gene or one normal chromosome and other dysfunctional genes. Undoubtedly, a person carrying two chromosomes each with single functional α-genes donates one normal genes to the progenies. It is, therefore, impossible to suffer their progenies from ‘hydrops fetalis’ as it occurs due to complete dysfunctioning of α-genes. DNA analysis of thalassaemia has revealed that non-function of both a genes on α single chromosome is only due to deletion of both genes from the chromosome.

Recent techniques have made it possible to detect α-thalassaemic couple for the presence of no gene chromosome. However, there is risk for giving birth to hydropic fetuses if both of the couple have α-thalassaemia due to no gene chromosome (Little, 1981). If there lies any possibility for gene therapy the patients are also suggested for the same. It has also been suggested that one should go to genetic counselor before marriage for safe and normal progeny.