Thalassemia is an inherited blood disorder that reduces the production of functional haemoglobin (the protein in red blood cells that carries oxygen. People with Thalassemia disease are not able to make enough haemoglobin, which causes severe anaemia. Haemoglobin is found in red blood cells and carries oxygen to all parts of the body.
By Prof. Dr. Abdullah G Arijo
When there is not enough haemoglobin in the red blood cells, oxygen cannot get to all parts of the body. Organs then become starved for oxygen and are unable to function properly.
Thalassemia and the haemoglobin disorder are the most common clinically serious single gene disorder in the world. About 60,000-70,000 children are born each year with a severe form of thalassemia. The majority are born in countries with limited resources where priority tends to be given to tackling high rates of infant and child mortality from infectious diseases and malnutrition. As a result, hereditary disorders receive little attention. Affected children of severe thalassemia often do not receive adequate treatment and die during childhood (Amin, 2011).
carrier detection procedures, genetic counselling, population screening and prenatal diagnosis of beta-thalassemia. Carrier detection can be made retrospectively, following the birth of an affected child or prospectively. Several programmes, to prevent homozygous beta-thalassemia, based on carrier screening and counselling of couples at marriage; preconception or early pregnancy, are operating in several Mediterranean at-risk populations. These programmes have been very effective, as indicated by increasing knowledge on thalassemia and its prevention by the target population and by the marked decline of the incidence of thalassemia major. Carrier detection is carried out by haematological methods followed by mutation detection by DNA analysis. Prenatal diagnosis is accomplished by mutation analysis on PCR-amplified DNA from chorionic villi. Prospects include automation of the process of mutation-detection, simplification of preconception and preimplantation diagnosis and fetal diagnosis by analysis of fetal cells in maternal circulation (Antonio Cao, 2002)
Genetic counsellors work as part of a health care team, providing information and support to families affected by or at risk of a genetic disorder. … In particular, genetic counsellors can help families to understand the significance of genetic disorders in the context of cultural, personal, and familial situations.
Hence, genetic counselling should be considered by couples who have one or more of the following risk factors: Abnormal results from routine prenatal testing. Amniocentesis results that identify a chromosomal defect. An inherited disease present in a close family member.
Genetic counselling is the communication process of providing information and support to individuals and families with a diagnosis and/or risk of occurrence of an inherited disorder. Culturally sensitive genetic counselling, with an emphasis on reproductive issues, is an integral and necessary component of comprehensive care for patients and parents affected by all forms of thalassemia disease and trait. Services should be provided by a licensed genetic counsellor in states with licensure legislation and by an ABGC board-certified or board-eligible genetic counsellor in all other states.
Genetic counselling is needed:
- at diagnosis and during adolescence
- before and after any genetic testing
- before pregnancy and/or as early in pregnancy as possible
- Annual follow-ups are needed to reinforce teaching.
Critical components of genetic counselling include:
- obtaining a three-generation genetic family history (pedigree)
- assessing risk for thalassemia in family members
- identifying risk factors impacting medical management (e.g., family history of other haemoglobin traits or diseases, hereditary hemochromatosis, G6PD deficiency, inherited thrombophilia, cardiovascular disease or its risk factors, cardiac conduction defects, diabetes, renal disease, ophthalmologic disorders, hearing loss, allergies, ethnicity, consanguinity)
- incorporating psychosocial information impacting the family system and relationships (e.g., location of residence, disclosure/nondisclosure of diagnosis, reliable source of emotional/social support)
- assisting patients in conveying information about genetic risk to other family members
- providing informed consent, pre-, and post-counselling for all genetic testing
- alpha-globin genotyping: haemoglobin H–Constant Spring and other structural alpha-globin variants, possible modifying effects of alpha-globin deletions/triplications on beta-thalassemia
- beta-globin genotyping: beta0/beta+, S, D, E, O, and other structural variants
The limitations of drawing genotype/phenotype correlations include:
- developmentally appropriate consent/education for minors
- reproductive genotype post–stem cell transplant or bone marrow transplant
- the possibility of revealing undisclosed adoption or alternative paternity
- discussing/facilitating appropriate screening and diagnostic tests for relatives
If HLA typing is performed when stem cell transplant or bone marrow transplant is an option, genetic counselling and education are vital due to ethical implications. A genetic counsellor should provide initial and ongoing teaching regarding natural history and clinical manifestations; signs and symptoms of a disease that warrant immediate medical attention; and available emotional and social support services. Genetic counsellors should also provide available resources in collaboration with outreach coordinators and social workers (e.g., research studies, support groups, advocacy organizations, and patient-to-patient or parent-to-parent connections).
Thus, a fatwa was issued by religious leaders permitting first-trimester abortion where a foetus is confirmed as having a serious disorder. A national network of DNA diagnostic laboratories is now being set up to make prenatal diagnosis available to all. Most Muslims accept that life does not begin at conception, believing that human life requiring perfection commences some weeks after development of the primitive streak11,12. Two renowned religious scholars in Pakistan gave a clear verdict permitting the termination of pregnancy before 120 days where the fetus is confirmed as having a serious disorder. Prenatal services aimed at the prevention of haemoglobin disorders are not yet comprehensive even in the most developed countries. The follow-up of children suffering from severe thalassemia despite the existence of prenatal diagnosis indicates that most births are not due to rejection of prenatal diagnosis, but rather patients’ and doctors’ unawareness of risk and services available. Poor service delivery is therefore a key ethical issue because it can deprive couples of the ability to make an informed choice.
In Bangladesh prevention of thalassemia can successfully be done by developing premarital screening through the primary health care system and mandatory blood test before marriage registration and counselling. At the same time, a prenatal diagnosis should also be made available nationwide as it is done in Iran. Ethical issues governing the generic counselling need to be addressed and uniform policy should be made taking into account the local, social and religious structures.
British genetic scholar Dr M. J. Denton warns that Sindh contains an enormous number of pedigrees with all sorts of genetic diseases.
There are families in Sindh suffering from cancer, diabetes, schizophrenia and other diseases.
He said that the diseases affected a larger number of families than in western countries and far more powerful for gene mapping than typical pedigrees in the West.
Speaking during a lecture programme on “Human genome potential of Sindh” at the Multimedia Centre of the Institute of the Information Technology University of Sindh on Wednesday, Dr Denton said that research figures were quite disturbing.
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Dr Denton, who is at present working as HEC’s foreign professor in the University of Sindh, said that genes were responsible for predisposing individuals to various common diseases of adulthood such as cancer, heart disease, diabetes, hypertension and schizophrenia.
He said that huge Sindhi pedigrees provided a unique and exceptionally valuable resource for gene mapping and could contribute greatly to our knowledge of human disease genes over the next few decades.
“They provide an opportunity for researchers in Sindh to play a role in the area of research with a major competitive advantage over their peers in western countries,” he said.
“This should enable them to generate world-class publishable results and greatly enhance their scientific careers”, he said.
The scholar said that his achievements in the field of retinal gene mapping borne out the fact that access to ideal genetic material was by far the major factor guaranteeing success.
He said that any gene mapping facility that had access to these wonderful pedigrees and set about systematically analyzing them was bound to generate new and useful insights into human genetics.
He said that gene mapping would also provide the genetic basis of human disease as well as further the research careers of Sindhi scientists and workers in the region.
The scholar said that there were compelling reasons for establishing a human gene-mapping facility in the University of Sindh because the university was at the geographical centre of Sindh surrounded by rural hinterland in which these remarkable families were to be found.
He said that the population of Sindh was now 40 million and it would grow to 60 million in the next two decades.
At present, Sindh’s population was equivalent to that of many large European countries and surely it justified setting up of at least one human gene-mapping facility in Sindh to help screen the disorders. The genetic diseases are a major cause of disability, death, and human tragedy in the world, said nearly 30 per cent of the world population suffer from cancer and 30 per cent from heart diseases, both influenced strongly by genetic factors which mean that burden of genes afflicted us all.
It is shocking to know that about seven per cent of all births are associated with a congenital abnormality, and 40 per cent infant mortality is attributed to genetic disease, 30 per cent of pediatric and 10 per cent of adult patients require hospital admission because of specific genetic disorders.
Mass awareness on cousin marriages and genetic counselling may help handle this issue or we should expect generations of genetically abnormal infants
Author :Prof. Dr. Abdullah G Arijo Chairman Department of Parasitology Sindh Agriculture University Tandojam