Genotypic and Phenotypic Composition of Sickle Cell Disease in the Arab Population - A Systematic Review

Abstract

Fateen Ata,1 Alaa Rahhal,2 Lujain Malkawi,3 Phool Iqbal,4 Ibrahim Khamees,5 Mousa Alhiyari,5 Zohaib Yousaf,6 Hana Qasim,7 Awni Alshurafa,8 Sundus Sardar,9 Saad Javed,10 Liam Fernyhough,8,11 Mohamed Yassin8 1Department of Endocrinology, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 2Department of Clinical Pharmacy, Hamad Medical Corporation, Doha, Qatar; 3Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Internal Medicine, Metropolitan Hospital, New York, NY, USA; 5Department of Internal Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 6Department of Internal Medicine, Reading Hospital - Tower Health, West Reading, PA, USA; 7Department of Internal Medicine, UMKC School of medicine, Kansas, MO, USA; 8Department of Medical Oncology /Hematology, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar; 9Department of Medicine, Division of Nephrology, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, PA, USA; 10Department of Internal Medicine, Icahn school of medicine at Mount Sinai/Queens Hospital Center, New York, NY, USA; 11Department of Medical Education, Weill Cornell Medicine – Qatar, Doha, QatarCorrespondence: Fateen Ata, Department of Endocrinology, Hamad general hospital, Doha, Qatar, Po Box 3050, Tel [phone], Email [email protected]; [email protected] Mohamed Yassin, Department of Medical Oncology /Hematology, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar, Tel [phone], Email [email protected]: Sickle cell disease (SCD) is a genetic disease influenced by ethnicity and regional differences in its clinical course. Recent advances in the management of SCD with newer therapies are being introduced to the Western population. However, many of these treatments are yet to be used in the Arabic SCD population. Understanding the genetic variations of SCD regionally is essential to anticipate the utilization of new treatments. This systematic review’s main objective is to pool the available data on the genetic composition of SCD in the Arabic population. Data for 44,034 patients was extracted from 184 studies (11 case reports, 8 case series, 56 retrospectives, 107 prospective observational studies, and 2 clinical trials) using PubMed, Scopus, and Google Scholar. Male (49%) and female (51%) patients were equally reported wherever gender was available (N=13105). Various SCD genotypes were reported in a total of 14,257 patients, including Hb SS (77%) Hb Sβ 0 (9.9%), and Hb Sβ+ (7.2%), while the rest of the genotypes, including HbSC, HbSD, HbSE, HbSO Arab, Hb S/α-Thal, Hb Sβ 0 + α-Thal, and HBS Oman were individually reported in < 4% of the cases. Major SCD complications in the Arab population included pain crises (48.25%) followed by neurological complications (33.46%), hepatobiliary complications (25.53%), musculoskeletal complications (24.73%), and hemolytic anemia (23.57%). The treatments reported for SCD included hydroxyurea (20%), blood transfusion (14.32%), and Deferasirox (3.03%). We did not find the use of stem cell transplantation or newer treatments such as L-Glutamine, Voxelotor, Crizanlizumab, or gene therapy reported in any of the studies included in our review. This review highlights the genetic makeup of SCD in Arab countries and its common phenotypic manifestations and will help direct further research on SCD in this region, especially concerning genetic therapy.Systematic Review Registration: The protocol has been registered in the International Prospective Register of Systematic Reviews(PROSPERO):CRD42020218,666. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=218666.Keywords: sickle cell disease, genotypes, SCD, sickle cell anemia, Arab

Keywords

• sickle cell disease
• genotypes
• scd
• sickle cell anemia
• arab.