Abstract: Background and Objective: The most common genetic disease in humans is hemoglobinopathies, also known as hemoglobin hereditary diseases. The purpose of this study was to look at the hemoglobinopathy patterns in anemic patients with a history of sickle cell disease in Saudi Arabia’s Eastern Province. Materials and Methods: This prospective cross-sectional study was conducted on anemic patients attending the hospital with a strong family history of hemoglobinopathy and general signs and symptoms, as well as mild to moderate anemia crises. One hundred and ten people were chosen to participate in this study. The research was carried out between September, 2019 and October, 2020. Results: The sickle cell trait was the most common hemoglobinopathy in males (31.1%) and sickle cell trait+beta thalassemia minor was the most common in females (18%). The gender of patients and the distribution of hemoglobinopathy types were found to have a significant relationship (p-value of 0.001). Conclusion: A significant correlation was discovered between the gender of patients and the distribution of hemoglobinopathy types. More efforts must be made to raise the prevention of endogamy awareness among Saudis.
INTRODUCTION
Hemoglobinopathies or hemoglobin genetic disorders, are the most frequent genetic disease in humans1. Because of their increased morbidity and mortality among affected persons, the international public health community has focused on two hemoglobinopathy disorders, thalassemia and sickle cell disease2,3. Some of these disorders, such as beta-thalassemia (β-thal) major, are classified as serious autosomal recessive phenotype disorders4. The β-thalassemia, Hb C disease, Hb E disease and sickle-cell disease are the clinically significant types5. The precise clinical picture in such a condition is mostly defined by an underlying genotype. The phenotype can display as a silent carrier, a calm state or moderate to severe anemia6,7.
The incidence of sickle cell disease and thalassemia in the Arab population is unknown, even though research findings have shown that these genetic disorders are relatively common in this region8. Several research findings in Saudi Arabia discovered that the incidence of these diseases differed considerably. Across the country, with the Eastern Province with the greatest incidence, accompanied by the Southwestern Provinces9. This increased incidence of hemoglobinopathies is similar to thestructure of autosomal recessive inherited disorders, which is evident in a country where endogamyaccounts for more than half of all marriages10,11.
Nonetheless, the value of neonatal screening programs is restricted because they can only provide secondaryprotection to sick children. Despite the fact that a prenatal screening program has the potential to reduce the occurrence of the disorder, many societies do not accept it. In this situation, a premarital screening program seems to have a high chance of lowering the occurrence of genetic conditions12. With these factors in mind, the Saudi Government decided to establish a mandatory premarital screening program in 2003 in order to decrease the occurrence of sickle cell disease and thalassemia13. The goal of this research was to evaluate the hemoglobinopathy patterns in anemic patients with a strong history of sickle cell disease in the Eastern Province, Saudi Arabia.
MATERIALS AND METHODS
Settings and participants of the study: This prospective cross-sectional study was conducted on anemic patients attending Health clinics with a strong family history of hemoglobinopathy and general signs and symptoms, as well as mild to moderate anemia crises. One hundred and ten people were chosen to participate in this study. The research was carried out between September, 2019 and October, 2020.
Sampling and HPLC technique: The CE-HPLC was used to analyze the hemoglobinopathy work-up (BioRad Laboratories, California, USA). Five milliliters of blood was collected in EDTA vacutainers and analyzed in batches within one week. On the Variant II Sampling Station (VSS), the samples were automatically mixed and diluted before being injected into the analytical cartridge. The dual pumps of the Variant II Chromatographic Station (VCS) deliver an ionic strength buffer gradient. The HbA2/F/S/H are isolated in the cartridge based on their ionic interaction with the cartridge substance. The isolated HbA2/F/S/H was then gonethrough the flow cell of the filter photometer, where the adjustments were evaluated. Variant II CDM (CDM) Software reduces original information from each assessment. The CDM generates a sample report and a chromatogram for each specimen, displaying all hemoglobin fragments eluted, their retention times, peak area andamounts of fractions14.
Ethical approval: The aim of the research was clearly addressed to the lab managers and the administrative unit provided informed consent to participate. Each participant provided written consent.
Statistical investigation: The Statistical Package for Social Sciences (SPSS) version 20 was used to examine the data. According to the type of variables, descriptive statistics (frequency, proportion estimation and mean) was used to tabulate and describe the data. Inferential statistics like the chi-square test and fisher exact test explain the association between age and gender prevalence of hemoglobinopathies. All statistical analyses were set at a 95% confidence interval (CI) and p<0.05 level of significance.
RESULTS
Table 1 showed that the percentage of males and females who participated in the study, as well as their age distribution. The percentage of female participants in the study was higher, at 56.6% than the percentage of male participants, at 43.4%. The most common age group among males and females was under 18 years old. There was no significant correlation between any of the age groups, gender, or the presence of hemoglobinopathy.
| Fig. 1: | Prevalence for hemoglobinopathy for both genders |
| Table 1: | Distribution of age and gender percentage in respondents participated in the study | ||||||||
| Gender |
Percentage (%) |
Age range |
Age Mean±SD |
<18 |
18-25 |
26-35 |
36-45 |
>46 |
Total |
| Male |
43.4 |
1-47 |
16.0±13.6 |
25 (46.3%) |
10 (66.7%) |
5 (25.0%) |
4 (33.3%) |
1 (25.0%) |
45 (42.9%) |
| Female |
56.6 |
1-52 |
21.0±14.3 |
29 (53.7%) |
5 (33.3%) |
15(75.0%) |
8(66.7%) |
3(75.0%) |
60 (57.1%) |
| Table 2: | Displays the distribution of hereditary hemoglobin disorders in both genders | |||||
|
Prevalence for hemoglobinopathies |
||||||
| Hemoglobinopathies |
Both gender (No./%) |
95% CI |
Male (No./%) |
95% CI |
Female (No./%) |
95% CI |
| Sickle cell disease+beta thalassemia trait |
2 (3.3) |
1.4-5.2 |
1 (1.6) |
0.3-2.9 |
1(1.6) |
0.3-2.9 |
| Sickle cell trait+beta thalassemia minor |
18 (29.5) |
24.7-34.3 |
7 (11.5) |
8.2-14.8 |
11 (18.0) |
14.0-22.0 |
| Sickle cell trait |
27 (44.3) |
39.1-49.5 |
19 (31.1) |
26.3-35.9 |
8 (13.1) |
9.6-16.6 |
| Minor increase of Hb F (stress, thyroidism) |
3 (4.9) |
2.6-7.2 |
0 (0.0) |
0 |
3 (4.9) |
2.6-7.2 |
| Beta thalassemia minor or intermedia |
1(1.6) |
0.3-2.9 |
0 (0.0) |
0 |
1 (1.6) |
0.3-2.9 |
| Hb H (suggestive) |
1(1.6) |
0.3-2.9 |
0 (0.0) |
0 |
1 (1.6) |
0.3-2.9 |
| Sickle cell disease+persistent of Hb F |
1 (1.6) |
0.3-2.9 |
1 (1.6) |
0.3-2.9 |
0 (0.0) |
0 |
| Sickle cell trait+beta thalassemia intermedia |
5 (8.2) |
5.3-11.1 |
1 (1.6) |
0.3-2.9 |
4 (6.6) |
4.0-9.2 |
| Beta thalassemia minor |
3 (4.9) |
2.6-7.2 |
1 (1.6) |
0.3-2.9 |
2 (3.3) |
1.4-5.2 |
| Total |
61(100.0) |
100-100 |
30 (49.2) |
44.0-54.4 |
31(50.8) |
45.6-56.0 |
Table 2 showed that the different types of hemoglobinopathy found in the patients who took part in the study, as well as their gender. The sickle cell trait was the most common hemoglobinopathy in males (31.1%) and the most prevalent in females was sickle cell trait+beta thalassemia minor, accounting for 18%. A significant relationship was discovered between the distribution of hemoglobinopathy types and the gender of patients (p-value of 0.001).
Figure 1 showed the prevalence of hemoglobinopathy in the study sample, with sickle cell trait representing the highest percentage of 44.3%, while beta-thalassemia minor or intermedia, hemoglobin H, sickle cell disease and persistent hemoglobin F constituted the lower percent (1.6%).
Table 3 presented the relationship between hemoglobinopathy prevalence and the age groups participating in the study. It turned out that there was no significant relationship between them (P-value 0.184), but we found that sickle cell trait and thalassemia minor were more prevalent (10%), specifically in the age group 26-35 years, while sickle cell trait was the most prevalent (15%), especially in the age group less than 18 years old.
| Table 3: | Illustrates the prevalence for hemoglobinopathy in age groups | |||||
|
Age groups (years)* |
||||||
| Hemoglobinopathies |
All age groups |
<18 |
18-25 |
26-35 |
36-45 |
>46 |
| Sickle cell disease+beta thalassemia trait |
2 (3.3) |
0 |
0 |
1 (1.7) |
1(1.7) |
0 |
| Sickle cell trait+beta thalassemia minor |
17(28.3) |
4 (6.7) |
2(3.3) |
6(10.0) |
2(3.3) |
3(5.0) |
| Sickle cell trait |
27(45.0) |
9(15.0) |
8(13.3) |
6(10.0) |
4(6.7) |
0 |
| Minor increase of Hb F (stress, thyroidism) |
3(5.0) |
0 |
0 |
3(5.0) |
0 |
0 |
| Beta thalassemia minor or intermedia |
1(1.7) |
1(1.7) |
0 |
0 |
0 |
0 |
| Hb H (suggestive) |
1(1.7) |
0 |
0 |
0 |
1(1.7) |
0 |
| Sickle cell disease+persistent of Hb F |
1(1.7) |
1(1.7) |
0 |
0 |
0 |
0 |
| Sickle cell trait+beta thalassemia intermedia |
5 (8.3) |
3 (5.0%) |
0 |
1(1.7) |
1(1.7) |
0 |
| Beta thalassemia minor |
3 (5.0) |
3 (5.0) |
0 |
0 |
0 |
0 |
| Total |
60(100) |
21(35.0) |
10 (16.7) |
17(28.3) |
9(15.0) |
3(5.0) |
| *Age group of study participants not statistically associated with hemoglobinopathies p = 0.184 | ||||||
DISCUSSION
The study was conducted among patients with a strong family history of sickle cell disease in order to detect other hemoglobin inherited disorders, as known hemoglobinopathies are centered in two geographical areas of Saudi Arabia: The Eastern and Southern Regions9. Since Saudi Arabia is mainly a tribal society with a significant number of endogomy marriages, recessive genes have occurred, accumulated and induced illness for centuries. This phenomenon has been identified as the primary cause of increased autosomal recessive disorder prevalence in similar populations15.
Many types of hemoglobinopathies associated with the sickle disease have been discovered in the current study, including all thalassemia types, Hb H and persistent Hb F. Results revealed that the proportion of female study participants was higher, at 56.6%, than the proportion of male study participants, which was 43.4%. Results showed that the most common age group among both males and females was under the age of 18, which was consistent with a previous study conducted by Alsaeed et al.16, which revealed a high rate of Hb variants in subjects aged <17 years old. In Saudi Arabia, there was no information on the impact of sickle cell diseaseon under-five mortality, there were few studies on death patterns. Furthermore, research findings from the Eastern Province revealed that 73% of mortalityoccurred in individuals under the age of 30, as a result of the respiratory syndrome. being the leading cause of death, followed by infection17. According to a recent WHOstatement, the most reliable measure to investigate the effects of sickle cell diseaseon public health was under 5 years old death18. The SCDkills approximately 5% of African children under the age of five, more than 9% in West Africa and up to 16% in person West African countries. Arising number of affected children stay alive to the age of five but were at risk of dying prematurely and 48% of patients who survive into adulthood have chronic organ failure19.
According to this study, sickle cell trait is the most common hemoglobinopathy in males (31.1%) and sickle cell trait+beta thalassemia minor is the most common in females (18%). The gender of patients and the distribution of hemoglobinopathy types were found to have a significant relationship. The reported incidence rate for sickle cell disease20 is 0.3-30%. Familial marriages were the most common cause of recessive hemoglobinopathies (homozygous or compound heterozygous mutations), which can increase the occurrence rate by up to 60%21. The prevalence of sickle cell disease and β-thalassemia in Saudi Arabia was thought to be among the highest in the Middle East (0.05 and 4.50%, respectively)21.
Sickle cell disease was a complex disorder with incidence ranging from 1-44% in different regions in India. Recurrent RBCsickling, causes hemolytic anemia, acute vaso-occlusion and organ failure22.
Numerous countries have launched various programs to increase public knowledge of hemoglobinopathies and monitor the incidence of hemoglobin disorders, for instance, thalassemia awareness campaigns in Cyprus, Greece and Italy have been effective23. However, in Italy, the initiatives and premarital consultation only participated ina provisional reduction in thalassemia cases in the 1970s and 1980s24.
In 2004, Saudi Arabia launched a program called premarital screening (PMS) and genetic counseling (PMSGC). The program’s objective was to decrease the couple's and progeny’s risk of genetic illnesses. The goal of these PMS and genetic counseling programs was to reduce the prevalence of hemoglobinopathy through the prevention of high-risk marriages. The PMS is a very valuable methodin health promotion and it is the only primary preventative measure in diseases like hemoglobinopathy, there were strong measures of increased knowledge on the importance of PMS in the identification and avoidance of genetic illnesses23.
CONCLUSION
The sickle cell trait was the most common hemoglobinopathy in males (31.1%) and sickle cell trait+beta thalassemia minor was the most common in females (18%). The gender of patients and the distribution of hemoglobinopathy types were found to have a significant correlation. More efforts should be made to raise preventive measures of endogamy awareness in the Saudi community.
SIGNIFICANCE STATEMENT
The sickle cell trait is the most common hemoglobinopathy in males and sickle cell trait+beta thalassemia minor is the most common in females. The gender of patients and the distribution of hemoglobinopathy types were found to have a significant correlation. This study will help the researcher to uncover the further efforts that should be taken in the Saudi community to raise endogamy prevention awareness.
ACKNOWLEDGMENT
This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University.