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Gene & Protein in Disease

REVIEW ARTICLE
Sickle cell disease: A 75-year journey

Samira Bolo , Tulika Mishra 2 , Uzoamaka Eziri , Tiara Calvo Leon 3 ,
1
1
Deepti Mankar 2 , Frank Navarrete 4 , Abrar Khan 2 , and Malpe Surekha Bhat *
5
1 American University School of Medicine Aruba, Oranjestad, Aruba
2 Department of Pathological Processes and Therapeutics, American University School of Medicine
Aruba, Oranjestad, Aruba
3 Department of Functional and Diagnostic Sciences, American University School of Medicine Aruba,
Oranjestad, Aruba
4 Department of Mind, Behavior and Global Health, American University School of Medicine Aruba,
Oranjestad, Aruba
5 Department of Nutritional, Biochemical and Molecular Sciences, American University School of
Medicine Aruba, Oranjestad, Aruba

Abstract

Sickle cell disease (SCD) is a disorder characterized by the polymerization of
hemoglobin chains in the deoxy-form, sickling of red blood cells, and hence vaso-
occlusive crisis, multiple organ damage, and increased mortality due to an inherited
defect in hemoglobin structure. SCD can also lead to a host of complications, which
include acute chest syndrome, avascular necrosis, stroke, pulmonary hypertension,
splenic sequestration, gallstones, deep vein thrombosis, pregnancy complications,
and end-organ damage. Complications are of varying complexities and can be as
*Corresponding author: grave as life-threatening. According to a report in 2005, the median life expectancy
Malpe Surekha Bhat for male and female patients with SCD in the United States (US) was around 42 and
(surekha.bhat@ausoma.org)
38 years, respectively. However, the survival rate of SCD patients in high-income
Citation: Bolo S, Mishra T, Eziri U, countries has steadily improved. Treatment options that were mainly for symptomatic
et al. Sickle cell disease: A 75-year
journey. Gene Protein Dis. relief and led to better well-being of the patient, containment of complication
2025;4(1):4361. recurrence, and decrease in mortality rates have evolved into curative treatment
doi: 10.36922/gpd.4361 options such as stem cell transplantations and gene therapy. The present paper is
Received: July 29, 2024 a review of the disease, its complications and implications on the community, and
1st revised: November 13, 2024 a historical tracking of the evolution of treatment options up to modern-day gene
2nd revised: December 4, 2024
3rd revised: January 14, 2025 therapy.
4th revised: January 22, 2025
Accepted: January 24, 2025
Published online: February 27, Keywords: Sickle cell disease; Treatments; Myeloablative transplantation; Gene therapy;
2025 Casgevy; Lentiviral
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
and reproduction in any medium,
provided the original work is Sickle cell disease (SCD) is a disorder characterized by the polymerization of hemoglobin
properly cited. chains in the deoxy-form, sickling of red blood cells (RBCs), and hence vaso-occlusive
Publisher’s Note: AccScience crisis, multiple organ damage, and increased mortality due to an inherited (autosomal
Publishing remains neutral with recessive) defect in hemoglobin structure. Normal adult hemoglobin (HbA) in
regard to jurisdictional claims in
published maps and institutional erythrocytes and reticulocytes is a tetrameric protein composed of four globin subunits
affiliations. (two α-globin and two β-globin). In SCD, the hemoglobin (HbS) is defective with an

Volume 4 Issue 1 (2025) 1 doi: 10.36922/gpd.4361