Medical Professionals

Abstract

Sickle cell disease (SCD), a distinctive and often overlooked illness in the 21st century, is a congenital blood disorder characterized by considerable phenotypic diversity. It comprises a group of disorders, with sickle cell anemia (SCA) being the most prevalent and serious genotype. Although there have been some systematic reviews of global data, worldwide statistics regarding SCD prevalence, morbidity, and mortality remain scarce. In developed countries with a lower number of sickle cell patients, cutting-edge technologies have led to the development of new treatments. However, in developing settings where sickle cell disease (SCD) is more prevalent, medical management, rather than a cure, still relies on the use of hydroxyurea, blood transfusions, and analgesics. This is a disease that affects red blood cells, consequently affecting most organs in diverse manners. We discuss its etiology and the advent of new technologies, but the aim of this study is to understand the various types of nutrition-related studies involving individuals suffering from SCD, particularly in Africa. The interplay of the environment, food, gut microbiota, along with their respective genomes collectively known as the gut microbiome, and host metabolism is responsible for mediating host metabolic phenotypes and modulating gut microbiota. In addition, it serves the purpose of providing essential nutrients. Moreover, it engages in direct interactions with host homeostasis and the immune system, as well as indirect interactions via metabolites. Nutrition interventions and nutritional care are mechanisms for addressing increased nutrient expenditures and are important aspects of supportive management for patients with SCD. Underprivileged areas in Sub-Saharan Africa should be accompanied by efforts to define and promote of the nutritional aspects of SCD. Their importance is key to maintaining well-being and quality of life, especially because new technologies and products remain limited, while the use of native medicinal plant resources is acknowledged.

Keywords: sickle cell, hemoglobin, anemia, microbiota, nutrition, vaso-occlusive crisis

1. Introduction

Sickle cell disease, an often overlooked disease in the 21st century, is a noncontagious and enduring congenital blood disorder. It encompasses a group of clinical syndromes that affect hemoglobin due to a genetic code for abnormal polymerized deoxygenated hemoglobin. This abnormal hemoglobin distorts the shape of red blood cells, and it is inherited by children from their parents [1]. The term sickle cell disease (SCD) is derived from the polymerization of two mutant sickle β-globin subunits leading to a crescent or sickled shape of erythrocytes [2].

Sickle cell disease comprises various genotypes, yielding a group of hemoglobinopathies [3]. The production of hemoglobin is regulated by the inheritance of a pair of genes, but there is considerable variability in absolute hemoglobin levels among patients with SCD [4]. Sickle cell anemia results from the inheritance of two sickle genes, with one gene from each parent [5,6].

Two parts, heme and globin, constitute the normal form of hemoglobin. The protein is made up of four polypeptide chains (two α chains and two β chains). There are many known mutations in the hemoglobin subunit β-HBB (β-globin protein) coding gene, which make up the most common form of hemoglobin in adult humans, hemoglobin A (HbA) [7]. A variety of inherited diseases arise from these mutations. Abnormal versions of β-globin, such as hemoglobin C (HbC), hemoglobin E (HbE), and hemoglobin S (HbS), are produced by a variant mutation in the HBB gene. It is this mutation in the HBB gene that causes sickle cell anemia [8].

Sickle cell anemia (SCA) is the most prevalent and serious genotype of SCD, followed by HbSC (“mild” form of SCA), hemoglobin (Hb) Sβ thalassemia, HbSβ+thalassemia (accounting for some 30–40% of SCD patients), and other rare and benign genotypes [9,10].

Sickled red blood cells are susceptible to chronic hemolysis [11], and emerging evidence reveals that SCD is made evident by the presence of chronic inflammation and oxidative stress, both of which play a role in the development of chronic vasculopathy and several other enduring complications [12]. SCA, characterized by abnormal red blood cells and hemoglobin, is worsened by low oxygen levels in the air [13].

SCA is manifested as the result of the presence of an autosomal recessive allele, which is found on the short arm of chromosome 11p15.5 [14]. This alteration of the genetic code leads to the substitution of a single amino acid, where valine replaces glutamic amino acid in the sixth position of the 146 amino acids of the β chain of hemoglobin [5] (Figure 1).

After more than one hundred years since the discovery of sickle cell group of hemoglobinopathies as genetically inherited diseases [15], new studies are still necessary to explore the molecular mechanisms leading to fetal hemoglobin induction and find ways to reduce the adverse effects in patients with SCA and other β-hemoglobinopathies [16].

There are both severe and mild SCD genotypes, which reflect the type of symptoms and prognoses for the disease. Research has been conducted during routine patient care to identify possible clinical biomarkers among SCD patients. These biomarkers may vary according to genotype and treatment categories. However, there is still insufficient progress in developing treatment options or counseling decisions [17,18,19].

Sickle-shaped red blood cells are more rigid and stickier, which leads to the obstruction of small blood vessels. This obstruction prevents oxygen from reaching body tissues and organs, inducing both acute and chronic intense pain. There is little research focusing on the pathophysiology of acute or chronic pain in SCD, and therefore it is still poorly understood. However, it is believed to be dependent on the interaction of several molecular mechanisms [2,20,21].

1.1. The Incidence of Sickle Cell Disease

This disease substantially induces multimorbidity and impairs quality of life, while placing strain on healthcare systems wherever it exists [22,23]. The global burden of this disease has been assessed [24], highlighting the high risk of child mortality associated with SCA. In Sub-Saharan Africa, it can contribute to as much as 90% of under-5 mortality [25,26], with approximately 500 children with SCD continuing to die prematurely every day [27]. This is due to delayed diagnosis and/or the lack of access to comprehensive care, a trend that urgently needs to be reversed [9].

Every year, between 300,000 and 400,000 newborns with SCA are delivered around the world, whereas tens of thousands of people show the homozygosity for hemoglobin S form, which represents the most severe clinical phenotype of the disease [28]. Although SCD occurs worldwide, Sub-Saharan Africa is the region with the highest prevalence. It is estimated that approximately 1000 children with SCD are born in Africa every day, and more than 500 of them die before reaching the age of 5 years [29].

Children suffer several preventable chronic disorders that are followed by premature death associated with SCD. Efforts have been made to identify achievable goals to improve outcomes both in the short and long term. These initiatives aim to recitfy the present unfair attention given to this inherited condition, particularly in developing countries [30].

Approximately 1 in 12 African Americans carries the SCD mutation, and 1 in 500 African Americans suffers from the disorder. In the U.S., 1 out of every 16,300 Hispanic-American neonates is born with SCA each year [31]. Epidemiological data on all blood disorders is still scarce, but SCD is estimated to affect approximately 250 million people globally.

Despite the increase in the global burden of SCD, which is believed to affect over 20 million people [32], including an estimated 200,000 annual sickle genotype births in Sub-Saharan Africa [33], available data on SCA prevalence, morbidity, and mortality remains limited on a global scale. However, some systematic reviews on global data exist [34,35].

Different areas in Côte d’Ivoire, Egypt, Lake Chad, Sudan, Lake Victoria, the coast of Kenya, Tanzania, Mozambique, and the east coast of Madagascar have been projected to have a a predicted HbS allele frequency between 7.5% and 12.5% [36]. In northern Mozambique, hematological studies have revealed a prevalence of sickle cell trait (HbAS) and G6PD (glucose-6-phosphate dehydrogenase) deficiency to be around 4% [37,38].

Sickle cell trait (HbAS) is notably more common in West Africa. It is very interesting and well-known that carriers of the sickle cell trait HbAS experience natural and nearly complete protection against severe Plasmodium falciparum malaria. This protection is observed despite the inadequately understood relationships between HbAS, malaria, and other common causes of child mortality [39,40,41,42].

1.2. Sickle Cell Disease Physiopathology

When cells are subjected to physiological stressors, they react with a mechanism described as the heat shock response. This mechanism activates a certain type of critical molecular regulator called heat shock proteins (HSPs) [43].

Heme oxygenase 1 is a member of the heat shock protein (HSP32) family and is involved in numerous cellular operations [44]. Increased heme in SCD causes the upregulation of heme oxygenase 1, which leads to cardiomyopathy through ferroptosis, an iron-dependent nonapoptotic form of cell death [45].

This enhances the fact that both genetic and environmental factors affect the process. Thus, the understanding of biomarkers and the molecular basis of diseases such as SCA are significant in playing a definitive role on the onset of such pathologies and, therefore, on the prevention strategies [46,47].

This leads to the formation of hemoglobin S and the change to sickle-shaped red blood cells compared to normal red blood cells. These cells obstruct the bloodstream, hence leading to serious problems, including cerebrovascular accident, nephropathy, retinopathy, infections, aches, and pains [48] (Figure 2).

Full Article: https://pmc.ncbi.nlm.nih.gov/articles/PMC10820494/