Public Awareness About Thalassemia in Khyber Pakhtunkhwa

GENETIC HETEROGENEITY OF THE B-GLOBIN GENE IN PESHAWAR KHYBER PAKHTUNKHWA PAKISTAN: A PILOT STUDY

By

Muhammad Adil (M.Phil. Scholar, Department of Biochemistry, UCSS, AWKUM)

Thalassemia is an inherited condition affecting the blood. Thalassemia is one of the major health problems worldwide. It is an autosomal recessive blood disorder, caused by DNA mutations that affect the synthesis of the globin protein. Hemoglobin in red blood cells serves the purpose of oxygen and carbon dioxide transport to all parts of the body. The patient who has thalassemia is not able to make enough hemoglobin and become anemic. Deficiency of hemoglobin results in reduced supply of oxygen to organs and become starved for oxygen and unable to perform normal body functions. Thalassemia is mainly grouped in two types; Alpha (α) thalassemia and Beta (β) thalassemia. Extensive research in this field have identified more the more than 200 different mutations on the α and β globin genes. Geographically these mutations are categorized based on ethnicity and racial origin. Thalassemia commonly found in malarial, tropic and sub-tropic region of Mediterranean countries, the Middle East, Transcaucasia, central Asian, the South and South east Asian countries.

Thalassemia is genetic disorder and is transmitted from parents to their offspring’s. If both parents are thalassemia carrier then there is 25% chance in each pregnancy that the child will inherit thalassemia, 50% chance that the child will be heterozygous for thalassemia and 25% percent chance that the child will be normal. If one of the parent is thalassemia carrier and one parent is normal having the capability to produce normal hemoglobin then there is no chance of thalassemia in offspring but 50% chance of normal pregnancies and 50% percent chance of pregnancies producing carrier children. In thalassemia patients becomes anemic due to the decreased production of hemoglobin by red blood cells. Other symptoms include pale skin, weakness, Fatigue, splenomegaly, jaundice and sometimes bones deformation. This abnormal hemoglobin although carries oxygen to all parts of the body, but are not able to release oxygen easily therefore the organs become starved for oxygen and the individual become anemic.

Pakistan being an under developed country and having close social and cultural values and continuous consanguineous marriages are constantly at high risk of genetic disorders. Consanguineous marriages account around 40% of thalassemia in Pakistan. Approximately 9.8 million carriers are estimated in total population of Pakistan with a carrier rate of 5–7%. In Pakistan forty thousand children are effect from thalassemia and about 5-9 thousands are added annually in a total of 200 million populations. The main causes of thalassemia in Pakistan are consanguineous marriages, high fertility rate, high birth rate, illiteracy, childhood marriages and lack of awareness about genetic disorders. In Pakistan thalassemia is most commonly prevailed in tribal belt and Khyber Pakhtunkhwa, but their concentration is also high in rural areas of Baluchistan, Sindh and Punjab provinces. In Pakistan as compared to a-thalassemia, β thalassemia is the most common disorder showing a wide range of heterogeneity.

In this case study, β-thalassemia patients’ blood samples were analyzed to find out the frequency of mutations in the population of the district Peshawar, Khyber Pakhtunkhwa. Amplification Refractory Mutation System (ARMS) based PCR were performed for known mutations from blood samples to investigate the prevalence of β-thalassemia mutations. The present study focused on these six common mutations and ARMS-PCR analysis was performed. Moreover, five mutations FSC-8/9 (+G), IVS-1-1 (G-T), IVS-1-5 (G-C), CD 41/42 (-TTCT), and CD15 (G-A) have been be detected in the district Peshawar region. The prevalence of each mutation in district Peshawar is summarized in table 1.

Table 1: Homozygous mutant allele frequency of different β-thalassemia mutation in district Peshawar

Serial No.	Mutation	Homozygous	Percentage
1	FSC 8/9, (+G)	10	43.5%
2	IVS-I-5, (G-C)	9	39.2%
3	CD 41/42, (-TTCT)	2	8.7%
4	IVS-I-1, (G-T)	1	4.3%
5	CD-15, (G-A)	1	4.3%
6	FSC-5, (-CT)	0	0.0%

To educate people about genetic disorders, Genetic counselors require to organize regular public seminars, workshops to highlight the significance of genetic testing and carrier screening. A pediatric genetic counselor is responsible for counseling the families’ having genetic disorders. The information provided by genetic counselor is aimed to help the affected families in making decisions, which helps in controlling genetic disorders. These decisions include various options such as birth control, mate selection and pre-natal testing. Prenatal screening is mainly concern to control and prevent the birth of new babies having risk of thalassemia major. This approach requires carrier screening of the parents with increased risk of thalassemia. As we are all aware of the fact that genetic disorders cannot be cured, earlier patients with β-thalassemia major were treated only with continuous blood transfusions. Nowadays, beside blood transfusions iron chelating therapy is combined to reduce iron load. Bone marrow transplantation is available but it’s very expensive and to find a suitable donor is also very challenging. Some medicines such as Hydroxyurea have also shown promising results on transfusion dependent β-thalassemia patients.

To significantly control the rate of thalassemia by comprehensive programs like public awareness, genetic counseling, carrier screening, pre-natal diagnosis, controlling the birth rate from the thalassemia affected or thalassemia carrier’s parents. To completely eradicated thalassemia it is highly recommended to adopting genetic screening certificate a pre-requisite before marriage and careful screening of pregnancies at risk are monitored.