Background: This study aimed to investigate the association between cousin marriages and the risk of Thalassemia major in Pakistan, while also assessing the awareness levels of affected patients regarding the disease and their inclination towards premarital carrier screening, prenatal diagnosis, and preconception genetic counseling.

Introduction: Thalassemia major stands as one of the most prevalent inherited diseases in Pakistan, attributed to various genetic defects hindering globin chain synthesis. With approximately 5000 new cases diagnosed annually and over 50,000 registered Thalassemia patients receiving treatment across the nation, the disease poses a significant public health concern.

Study Design: A descriptive cross-sectional study was conducted at the Thalassemia blood center, Hilal-e-Ahmer trust hospital in Sargodha, from March 2022 to October 2022. A pretested predesigned close-ended questionnaire was utilized to collect data from a sample size of 200 participants, comprising Thalassemia patients resulting from cousin and non-cousin marriages. The study obtained approval from the ethical review committee of the institution before commencement.

Results: Our findings revealed a slight male predominance, with 54% males and 46% females. Cousin marriages accounted for 79% of patients, highlighting the significant influence of genetic factors in Thalassemia major prevalence. Among families, cousin marriage was prevalent in 86% of cases. Additionally, 52% of parents of Thalassemia patients became aware of their carrier status after undergoing screening.

Conclusion: The high prevalence of cousin marriages in our sociocultural context contributes to the persistent increase in Thalassemia major cases. Furthermore, inadequate awareness among affected individuals underscores the need for comprehensive education initiatives targeting the general public, parents, and families of Thalassemia patients.

Thalassemia major, consanguineous marriages, screening tests

Lai K, Huang G, Su L, He Y. The prevalence of thalassemia in mainland China: Evidence from epidemiological surveys. Scientific Reports. 2017;7:920. doi:10.1038/s41598-017-00967-2.

Mausumi B. A study on knowledge, attitude and practice about thalassemia among the general population in the outpatient department at a tertiary care hospital of Kolkata. JPM &HH. 2015;1(1):5-12.

Shariq M, Moiz B, Zaidi N, et al. Pre-marital screening for β thalassemia in Pakistan: An insight. J Med Screen. 2014;21(3):163–164. doi:10.1177/0969141314532935.

Tazeen M, Mohammed Adil A, Ujala N, Muhammad Safwan R, Jovaria M. Frequency of β-thalassemia trait in families of thalassemia major patients, Lahore. JAMCA. 2013;25(3-4):58-60.

Zarei T, Razavi Z, Beiranvand R. Epidemiology of thalassemia and recent prevention and management strategies. International Journal of Hematology-Oncology and Stem Cell Research. 2019;13(3):158–167. doi:10.18502/ijhoscr.v13i3.658

Bittles AH. Consanguinity and its relevance to clinical genetics. Clinical Genetics. 2001;60(2):89–98. doi:10.1034/j.1399-0004.2001.600201.x

Ansari SH, Shamsi TS, Ashraf M, Bohray M, Farzana T, Khan MT, et al. Molecular epidemiology of β-thalassemia in Pakistan: Far-reaching implications. Int J Mol Epidemiol Genet. 2011;2:403–8. doi:10.1038/tpj.2014.68.

Qurat-Ul-Ain L, Laiq A, Muhammad H, Shahid MR, Farhat J. Prevalence of β-thalassemia patients associated with consanguinity and anti-HCV antibody positivity–a cross-sectional study. Pak J Zool. 2011;43(1):29-36.

Tadmouri GO, Nair P, Obeid T, Al Ali MT, Al Khaja N, Hamamy HA. Consanguinity and reproductive health problems among Arabs. Reprod Health. 2009;6:17. doi:10.1186/1742-4755-6-17.

Moiz B, Azam I, Moatter T, Hasan SH, Ali SH. Genetic counseling and prenatal diagnosis in Pakistan: Experiences and reflections from a diverse population. J Genet Couns. 2015;24(6):976–984. doi:10.1007/s10897-015-9840-4.

Saeed U, Piracha ZZ. Thalassemia: Impact of consanguineous marriages on most prevalent monogenic disorders of humans. Asian Pacific Journal of Tropical Disease. 2016;6(10):837–840. doi:10.1016/j.apjtb.2016.08.001.

Kanaan ZM, Mahfouz R, Tamim H. The prevalence of consanguineous marriage in an underserved area in Lebanon and its association with congenital anomalies. Genet Test. 2008;12(3):367–372. doi:10.1089/gte.2007.0101.

Alwan A, Modell B. Community control of genetic and congenital disorders. WHO Regional Office for the Eastern Mediterranean, Alexandria, Egypt. 1997.

Rafique B, Moinuddin A. Haemoglobinopathies and interfamily marriage in Pakistan. Pak Paedi J. 1991;15:123-131.

Nashwan AA, Al Qadrah A, Al Khaldi N. Challenges in the management of beta-thalassemia: A report of 23 patients. Journal of Taibah University Medical Sciences. 2019;14(2):174–179. doi:10.1016/j.jtumed.2018.12.007.

Mahato RK, Tamang MK, KC S. Psychosocial aspects of thalassemia: A systematic review of literature. Journal of Hematology & Oncology. 2019;12(1):1–10. doi:10.1186/s13045-018-0682-7.

Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: a systematic analysis. JAMA Oncol. 2022;8(3):420-44.

Tran KB, Lang JJ, Compton K, Xu R, Acheson AR, Henrikson HJ, et al. The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022;400(10352):563-91.

Sharma R, Abbasi-Kangevari M, Abd-Rabu R, Abidi H, Abu-Gharbieh E, et al. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7(7):627-647. doi:10.1016/S2468-1253(22)00032-5.

Alvarez EM, Force LM, Xu R, Compton K, Lu D, Henrikson HJ, et al. The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Oncol. 2022;23(1):27-52. doi:10.1016/S1470-2045(21)00361-7.

Da Cunha AR, Compton K, Xu R, Mishra R, Drangsholt MT, Antunes JLF, et al. The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories: A systematic analysis for the global burden of disease. JAMA Oncol. 2023;9(10):1401-1416. doi:10.1001/jamaoncol.2022.7021.

Nejadghaderi SA, Moghaddam SS, Azadnajafabad S, Rezaei N, et al. Burden of thyroid cancer in North Africa and Middle East 1990–2019. Front Oncol. 2022;12:955358. doi:10.3389/fonc.2022.955358.

Abbasi-Kangevari M, Moghaddam SS, Ghamari SH, et al. The burden of prostate cancer in North Africa and Middle East, 1990–2019: Findings from the global burden of disease study. Front Oncol. 2022;12:961086. doi:10.3389/fonc.2022.961086.

Azadnajafabad S, Moghaddam SS, Mohammadi E, Rezaei N, et al. Burden of breast cancer and attributable risk factors in the North Africa and Middle East region, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Front Oncol. 2023;13:1132816. doi:10.3389/fonc.2023.1132816.

Piracha ZZ, Saeed U. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer. J Cancer Res Ther.

Collaborative R, Zaborowski AM, Abdile A, Adamina M, Aigner F, et al. Characteristics of early-onset vs late-onset colorectal cancer: a review. JAMA Surg. 2021;156(9):865-874. doi:10.1001/jamasurg.2021.3660.

Ikuta KS, Swetschinski LR, Aguilar GR, Sharara F, Mestrovic T, Gray AP, et al. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022;400(10369):2221-48. doi:10.1016/S0140-6736(22)01944-4.

Blach S, Terrault NA, Tacke F, Gamkrelidze I, Craxi A, Tanaka J, et al. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol. 2022;7(5):396-415. doi:10.1016/S2468-1253(21)00468-4.

Sheena BS, Hiebert L, Han H, Ippolito H, Abbasi-Kangevari M, et al. Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7(9):796-829. doi:10.1016/S2468-1253(22)00220-4.

Azhar A, Saeed U, Piracha ZZ, Amjad A, Ahmed A, Batool SI, et al. SARS-CoV-2 related HIV, HBV, RSV, VZV, Enteric viruses, Influenza, DENV, S. aureus and TB co-infections. Arch Pathol Clin Res. 2021;5(1):026-033. doi:10.15436/2381-1964.21.392.

Piracha ZZ, Saeed U. Global emergence of Langya virus: A serious public health concern. J Global Health. 2023;13.

Piracha ZZ, Saeed U, Tariq MN, Gilani SS, Rauf M, Ghyas H, et al. Emerging One Health Preparedness to Combat National Burden of Diseases in Pakistan: A Comprehensive Insight. J Community Med Health Sol. 2023;4(2):080-088. doi:10.15436/2381-1964.23.279.

Piracha ZZ, Tariq MN, Rasool M, Gilani SS, Saeed U, Rana MSF, et al. Catalyzing Global Action: Addressing SARS-CoV-2 Vaccine Hesitancy, Knowledge Disparities, and Epidemic Preparedness Challenges in Pakistan. Biomed J Sci & Tech Res. 2022;52(3):43702-43707. doi:10.26717/BJSTR.2022.52.004349.

Uppal SR, Uppal R, Khan AA, Saeed U, Piracha ZZ, Ali Z. Estimating the Prevalence of Fungal Nail Infections and Potential Concerns for Central Disease Surveillance Hub in Pakistan. Arch Clin Biomed Res. 2022;6(3):462-465. doi:10.15436/2381-1964.22.362.

Uppal SR, Khan AA, Uppal R, Saeed U, Piracha ZZ, Uppal R. Rising Surge of Antimicrobial Resistance and Urinary Tract Infections in Pakistani Children: A Potential Life-Threatening Scenario. Fortune J Health Sci. 2022;5(2):281-283. doi:10.15436/2381-1964.22.290.

Micah AE, Bhangdia K, Cogswell IE, Lasher D, Lidral-Porter B, et al. Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026. Lancet Global Health. 2023;11(3):e385-e413. doi:10.1016/S2214-109X(22)00527-7.

Saeed U, Piracha ZZ, Uppal SR, Waheed Y, Uppal R. SARS-CoV-2 induced hepatic injuries and liver complications. Front Cell Infect Microbiol. 2022;12:726263. doi:10.3389/fcimb.2022.726263.

Saeed U, Piracha ZZ, Uppal R, Uppal R. SARS-CoV-2-Associated CRP, DD, FER, HBA1c, IL6, LDH, PBNP, and PCT biomarkers and high-resolution computed tomography during the first three waves of COVID-19 in Pakistan (2019…). Jundishapur J Microbiol. 2023;15(1).

Saeed U, Piracha ZZ, Uppal R, Khan AA, Rasheed A, Waheed A, et al. Evaluation of SARS-CoV-2 spike antibody levels among Sputnik V first dose vaccinated people in Pakistan: formulation of national anti-COVID-19 mass vaccination strategy. Arch Clin Biomed Res. 2023;6(01):209-216. doi:10.3390/jdb2020050.

Saeed U, Piracha ZZ, Ashraf H, Tasneem S, Uppal SR, Islam T, et al. Effectivity analysis of COVID-19 vaccines against emerging variants of SARS-CoV-2. Arch Clin Biomed Res. 2023;6(01):209-216. doi:10.3390/jdb2020050.

Saeed U, Piracha ZZ, Kanwal K, Munir M, Waseem A, Nisar T, et al. Contemplating SARS-CoV-2 infectivity with respect to ABO blood groups. Int J Clin Virol. 2023;5(2):082-086. doi:10.3390/jdb2020050.

Marghoob M, Saeed U, Piracha ZZ, Shafiq H, Fatima N, Sarfraz N, et al. SARS-CoV-2 Infection and Incidence of Mucormycosis. Arch Clin Biomed Res. 2023;6(1):41-49. doi:10.3390/jdb2020050.

Piracha ZZ, Saeed U, Sarfraz R, Asif U, Waheed Y, Raheem A, et al. Impact of SARS-CoV-2 on Onset of Diabetes and Associated Complications. Arch Clin Biomed Res. 2023;6(1):217-227. doi:10.3390/jdb2020050.

Nadeem H, Ayesha M, Saeed U, Piracha ZZ, Tahir R, Mehtab F, et al. SARS-CoV-2 infection-associated detrimental effects on the various human organs. Int J Clin Virol. 2023;5(2):072-081. doi:10.3390/jdb2020050.

Hannan H. Consanguineous marriages: Preconception consultation in primary health care settings. J Community Genet. 2012;3(3):185–192. doi:10.1007/s12687-012-0087-0.

Khalid N, Noreen K, Qureshi FM, Mahesar M. Knowledge of thalassemia and consanguinity: A multicenter hospital-based retrospective cohort study from the metropolitan city of Karachi, Pakistan. Pak Med J. 2019;35(4):868–872. doi:10.12669/pjms.35.4.457.

Sundus A, Shamaila S, Saima M. Screening of thalassemia trait in parents of beta-thalassemia major patients in district Kohat, Pakistan. Gomal Journal of Medical Sciences. 2013;11(2):242–245.

Abbasi-Kangevari M, Derakhshani S, Saeed U, Piracha ZZ, Amini E, Khan AU. Breast Cancer-Associated Immune Checkpoints and Therapeutic Implications. Curr Drug Targets. 2023;25(5):546-554. doi:10.2174/1389450140666220218103435.

Aamir U, Khan AA, Saeed U, Piracha ZZ, Uppal R, et al. Emerging new drug resistance and therapeutic strategies against Mycobacterium tuberculosis. Antibiotics (Basel). 2022;11(6):648. doi:10.3390/antibiotics11060648.

Piracha ZZ, Saeed U, Khan AA, Uppal R, Uppal R. SARS-CoV-2-Associated Myocardial Injury and Cardiovascular Implications. Front Cardiovasc Med. 2022;8:796798. doi:10.3389/fcvm.2021.796798.

Piracha ZZ, Saeed U, Uppal R, Kanwal K, Uppal SR, et al. Evidence-based Therapeutic Options for Coronavirus Disease 2019 (COVID-19). Antibiotics (Basel). 2021;11(1):35. doi:10.3390/antibiotics11010035.

Piracha ZZ, Saeed U, Uppal R, Uppal R. A comprehensive review of pathophysiology, clinical symptoms, and therapeutic options for novel coronavirus disease 2019 (COVID-19). Antibiotics (Basel). 2021;10(9):1245. doi:10.3390/antibiotics10091245.

Piracha ZZ, Saeed U, Kanwal K, Uppal R, Uppal R. Immunology, serology, and novel therapeutic strategies for coronavirus disease 2019 (COVID-19). Antibiotics (Basel). 2021;10(10):1142. doi:10.3390/antibiotics10101142.

Piracha ZZ, Saeed U, Waheed Y, Uppal SR, Khan AA, et al. Emerging treatment strategies and drug candidates for COVID-19: A systematic review. Front Pharmacol. 2021;12:651783. doi:10.3389/fphar.2021.651783.

Piracha ZZ, Saeed U, Uppal R, Uppal R. Non-Pharmacological Treatment Strategies for COVID-19. Arch Biomed Res. 2021;7(3):234-237. doi:10.30954/2277-2426.03.2021.1.

Piracha ZZ, Saeed U, Uppal R, Uppal R. Clinical presentations, pathophysiology, and therapeutic options for COVID-19. Int J Clin Virol. 2021;5(1):010-019. doi:10.3390/ijcv5010004.

Piracha ZZ, Saeed U, Uppal R, Uppal R. Etiology, pathogenesis, clinical presentations, and treatment options for COVID-19. Int J Clin Virol. 2021;5(2):036-045. doi:10.3390/ijcv5010004.