INTRODUCTION

Hemoglobinopathies, genetic diseases related to hemoglobin synthesis, constitute the most common monogenic disorders worldwide. The genetic cause of this group of diseases is variants in the globin genes that encode the globin chains of the tetrameric hemoglobin protein. These DNA variants can lead to altered synthesis of α- or β-globin (α- and β-thalassemia syndromes, respectively) or to structural changes in hemoglobin, causing diseases such as sickle cell disease, hemolytic anemia, erythrocytosis, or polycythemia [1]. Approximately 7% of the world's population trait a DNA variant that causes a defect in hemoglobin synthesis, resulting in approximately 300,000 to 400,000 affected newborns; the majority of these have sickle cell syndrome and a small proportion have transfusion-dependent β-thalassemia major [2].

Abnormal hemoglobins are formed because of gene mutations such as point mutations, nucleotide additions, and nucleotide deletions. More than 90% of known abnormal hemoglobin types are caused by a single amino acid change in a globin chain, and 60% of these occur in the beta globin chain of hemoglobin [3]. Hemoglobin S, Hemoglobin D, Hemoglobin C, and Hemoglobin E are the most common pathological hemoglobins in Turkey in order of frequency [4]. Currently, hemoglobin variant analysis is primarily performed with HPLC (high-performance liquid chromatography) analysis. In clinical laboratories for hemoglobinopathies, capillary electrophoresis, classical electrophoresis, and genetic methods are also used in analysis [5].

There are two β-globin genes in the genome of each individual, one on each homologous chromosome on chromosome 11. If there is one faulty β-globin gene, β-thalassemia minor or β-thalassemia trait occurs, and if both genes are faulty, β-thalassemia major disease occurs. Laboratory findings of β-thalassemia minor Hb electrophoresis shows an increase in HbA2 from 3.5% to 7% in more than 90% of cases, and this finding is diagnostic [6].

Although clinicians easily recognize severe forms of hemoglobinopathies, traits can be easily overlooked. Traits are usually asymptomatic and are only detected incidentally during family analysis due to an affected family member, during participation in hemoglobinopathy screening programs, or during routine hematological or biochemical analysis such as diabetes-related HbA1c analysis by HPLC or capillary electrophoresis. Molecular analysis of globin genes will support the definitive diagnosis of patients, traits, and those presenting with atypical hematological parameters [7, 8].

Studies have found the frequency of beta thalassemia traits in Turkey to be approximately 2.1% [9, 10] and the frequency of abnormal hemoglobin to be 1% [2]. In our study, we aimed to contribute to the literature by determining the frequency of beta thalassemia traits and abnormal hemoglobin variants in our central laboratory.

MATERIAL AND METHODS

The study was approved by the University of Healty Science, clinical research ethics committee (no: 13/13, date: 14.11.2024).

In our study, hemoglobin variant analysis data performed in our hospital's central laboratory between November 1, 2020 and July 31, 2024 were retrospectively obtained from the Laboratory information management system (LIMS). Samples of patients of both genders between the ages of 6 months and 99 years were included in the study. Samples of the same patient at different times and samples of patients aged 0-6 months whose HbF levels had not returned to normal were not included in the study. The number of abnormal hemoglobins for Hemoglobin S, D, C and E in the specified time period was determined as a percentage by dividing it into the total number of patients who underwent hemoglobin variant analysis. Those with HbA₂ > 3.5% were considered to be beta thalassemia traits [10, 11]. Hemoglobin variant analysis was performed using a cation exchange HPLC-based Adams HA-8180T (Arkray, Inc., Japan) device.

RESULTS

The number of samples studied for hemoglobin variant analysis was 223,609. In our study, we examined the frequency of 4 variant types, namely Hemoglobin S, D, C and E (Table 1). Abnormal hemoglobin variants such as Hemoglobin S, D, C and E were detected in 0.35% of the samples included in the study (800 cases). Of these, Hb S (0.15%) was detected in 356 cases, Hb D (0.13%) in 302 cases, Hb C (0.05%) in 117 cases and Hb E (0.01%) in 25 cases. The HbA2 level of 6017 patients was 3.6 and above. We determined the frequency of beta thalassemia traits as 2.69% (Table 2).

DISCUSSION

Hemoglobinopathies are blood diseases caused by structural changes or synthesis disorders in the polypeptide chains of the hemoglobin molecule and are examined in two parts as thalassemia and abnormal hemoglobins [12]. In our study, we examined the abnormal hemoglobins and patients with HbA₂ >3.5 from the laboratory information system to determine the frequency of beta-thalassemia traits and abnormal hemoglobins in our central laboratory.

In our study, 0.35% (800 cases) of the 223,609 hemoglobin variant analysis samples we screened in our central laboratory were detected to have abnormal hemoglobin variants such as Hemoglobin S, D, C and E. Of these, Hb S was detected in 356 patients (0.15%), Hb D in 302 cases (0.13%), Hb C in 117 cases (0.05%) and Hb E in 25 cases (0.01%). We have reviewed various studies on the subject. Among these, Dikker et al. [4] analyzed 1894 cases with HPLC in their laboratory and found abnormal hemoglobin variants in 0.95% (18 cases). They observed Hb S most frequently and then HbD variant more frequently.

In a study conducted by Güvenç et al. [13] in Adana, the frequency of abnormal hemoglobins was found to be 6.8%, with the most frequent being Hb S, Hb D and Hb E. Oğuz et al. reported the most frequent abnormal hemoglobins in our country as HbD, HbS, HbE, HbC in their study [14]. Different abnormal hemoglobins may be seen and found in different percentages among the studies. The most important reason for this may be differences in abnormal hemoglobin frequency due to the ethnic structure specific to the region, the frequency of consanguineous marriages and the presence of foreign patients coming from different countries. Our study is important in terms of determining the frequency of abnormal hemoglobin in our province. In addition, the frequency of occurrence of these abnormal hemoglobins will help predict abnormal variants that may be encountered in laboratory practice.

We also evaluated the frequency of beta thalassemia in our study. In our study, 6017 patients had HbA₂ levels of 3.6 and above out of 223,609 hemoglobin variant analysis samples that we screened in our central laboratory. We determined the frequency of beta thalassemia traits as 2.69%. Although the frequency of beta thalassemia traits is generally 2.1%, it varies between 0.6% and 10.7% depending on the region [14]. Akağaç et al. [10] reported the frequency of beta thalassemia traits as 3% in Uşak city. Keskin et al [15] reported the beta-thalassemia trait frequency as 3% in Denizli. Güvenç et al [13] reported the beta-thalassemia trait frequency as 13.46% in Adana. There may be differences in the frequency between studies for beta-thalassemia trait. The reason for this difference may be related to the ethnic structure specific to the region and the high number of consanguineous marriages.

As a result, we detected abnormal variants in our study, most frequently Hb S, followed by HbS, HbD, HbC and HbE in order of frequency. We detected abnormal hemoglobin in our study at a lower frequency than reported in studies in the literature. We detected beta thalassemia traits at a similar percentage to the rates reported in the literature. It should not be forgotten that the HPLC method is a screening test for hemoglobinopathies and that definitive diagnosis can be made with genetic methods. Our study will contribute to the predictability of the frequency of beta thalassemia traits and pathological hemoglobin.

CONFLICT OF INTERESTS

The authors have no conflict of interest to declare. The authors declared that this study has received no financial support.

REFERENCES

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Notas de autor

huseyin.dag@sbu.edu.tr

Información adicional

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