بتا تالاسمی

Thalassemia screening instructions in Iran consider couples with MCV = 75-80, MCH = 26-27, HbA2<3.5, and HbF<3 indices as low-risk couples, and therefore further genetic testing is not obligatory. If the blood indices of alpha thalassemia carriers (One alpha gene deletion or two alpha gene deletions) fall within the parameters of low-risk couples, the identification of such couples within the beta thalassemia screening program will not be feasible. However, if the blood indicators of alpha thalassemia carriers fall within the range of the suspected high-risk couple, these couples can be identified through beta thalassemia screening instructions.

In this cross-sectional study, information was extracted from 2359 individuals diagnosed with alpha thalassemia, identified between 2018 and 2021, in 22 marriage counseling centers in Isfahan province using the results of the PND test. The blood indices MCV and MCH of alpha thalassemia carriers were compared with the low-risk and high-risk values of beta thalassemia carrier couples.

The average MCH and MCV of couples affected by alpha thalassemia gene deletions 1 and 2 are respectively within the low-risk and high-risk ranges for beta-thalassemia.

Beta thalassemia screening guidelines can effectively identify individuals with two alpha thalassemia gene deletions, although they have no effect in identifying those with one alpha gene deletion. Current guidelines indicate that it is possible to prevent the occurrence and complications of pregnancy in mothers with Bart's hemoglobin infants; however, the identification of H hemoglobin disease remains unfeasible.

Thalassemia is an autosomal recessive hereditary disease that occurs due to a decrease in the synthesis of Please recheck. In beta thalassemia, defects in β-globin synthesis lead to an imbalance of β- and α-globin chains and the accumulation of α4 chains in the erythroid precursor which leads to ineffective erythropoiesis, shortened red blood cell survival, and finally clinical symptoms such as delayed sexual and physical maturation, endocrine dysfunction, cardiomyopathy, liver disease, bone deformities and hepatosplenomegaly. Current treatments such as transfusion, iron chelating agents and allogeneic stem cell hematopoietic transplantation have limitations in their use, including iron overload, lack of a human leukocyte antigen (HLA) matched compatible donor, and graft versus host disease (GVHD). Gene therapy is a new therapeutic option for beta thalassemia patients that induces the continuous expression of beta globin chains in the patient’s hematopoietic stem cells. The idea of gene therapy was first proposed in the early 1970s, and the ultimate goal of this treatment method is to express the defective gene in the target cell in a way that can reduce the symptoms of the disease or eliminate them (symptoms) altogether. There are two general methods for gene therapy: the integrating vector, in which the desired gene is inserted into the genome of the target cell and its lifelong expression follows, is the non-integrating method, in which the vector doesn’t integrate into the genome of the target cell and the cytoplasmic form enables gene expression. The first beta thalassemia gene therapy was performed in France in 2006, and in this clinical trial, the first patient with the E/β0 thalassemia was treated at the age of 18. Gene therapy for beta-thalassemia has been approved by the food and drug administration in 2022 for patients aged 12 years and older who have a non β0/β0 phenotype. It seems that this therapeutic option is the definitive treatment method for blood transfusion-dependent beta-thalassemia patients.  However, this treatment method still has limitations: high cost, sensitivity of lentiviral vector production, and the possibility of integration of the vector near the proto-oncogene and its activation are some of them.

Thalassemia is the most common monogenic disease worldwide inherited in autosomal recessive manner. Beta-thalassemia is caused by mutations in beta-globin gene. It is characterized by reduction in red blood cell indices including low MCV, low MCH, high RBC count, low HbA1 and high HbA2. Considering these symptoms, finding a relation between erythrocyte indices and kind of mutations can be used as a rapid method in mutation diagnosis and initial screening of carriers.

In this descriptive-analytical study after DNA extraction from 200 beta- thalassemia minors in Khuzestan province by salting out method, we amplified and sequenced beta-globin gene by Sanger sequencing. Finally, we analyzed statistically the beta-globin gene mutations and erythrocyte indices association by SPSS.

Our results showed that IVSII-1(G > A) is the most common mutation with 22.5% frequency in this population of beta-thalassemia carriers. We found that MCV index variations have a meaningful association with beta-globin gene mutations and the highest mean of MCV (65.4 ± 3.7) was observed in IVSI-110(G > A) mutation.

The results comply with many other studies performed in this field and can be used for rapid detection of mutation in carrier parents and prenatal diagnosis.

Beta thalassemia is one of the most common hereditary diseases in Iran. The birth of a child with thalassemia causes many social and economic problems for parents and the health care system. Nowadays, prenatal screening programs to detect beta thalassemia have received much attention in the country. The aim of the present study was the determination and sampling of chorionic villi for the diagnosis of beta-thalassemia major in the first trimester of pregnancy in south-western Iran.

The present descriptive-prospective and practical study was conducted in 2021 on couples suffering from thalassemia minor and referred to the Narges Genetics Laboratory in Ahwaz, Iran. For preventive measures, blood samples were taken from volunteers. At that point, the couples who had HbA2 above 3.5 and were in the 10th to 13th week of pregnancy continued the treatment by performing chorionic villus sampling in order to evaluate the health of the fetus. Chorionic villus sampling was performed under local anesthesia with a needle from the abdominal area of pregnant women, and about 5-10 cc of placental trophoblast villi were collected. The collected data were analyzed using t-test and chi-square statistical tests.

A total of 91 pregnant women underwent chorionic villus sampling. Thirty-eight individuals (41.8%) had thalassemia minor, 25 individuals (27.5%) had thalassemia major, the familial relationship between couples was also examined, and there was no significant association between the familial relationship and occurrence of thalassemia major. 20 people (30%) had a child with thalassemia major and 60 people (66%) had a child with thalassemia minor. Fetuses with thalassemia major in mothers with blood type A+, 38 subjects (42%) and O+ 35 subjects (38.4%), the prevalence of thalassemia major was higher in the Fars subjects, the highest in 39 subjects (42.8%), and the lowest was the Kurdish people with one person (1 percent).

The technique of chorionic villus sampling is an accurate method with no significant risk to both mother and fetus. This method can be used to diagnose beta thalassemia before birth.

Thalassemia has been classified by the World Health Organization (WHO) as a major public health problem. Meanwhile, hyperthyroidism is a serious complication and is thought to be associated with iron overload in patients with thalassemia major. The current study aimed to study the function of the thyroid gland in beta-thalassemia major patients who attended the thalassemia center in Mofid children's hospital of Tehran, Iran.

The present descriptive study carried out between 2019-2020 to evaluate the function of the thyroid gland in 40 children with beta-thalassemia major aged between 15-2 years.The demographical information of all the patients was collected and the serum total triiodothyronine (T4), ferritin, and thyroid-stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assay (ELISA). All data were included in SPSS columns and were analyzed using descriptive statistics and Chi-square test, t-test, and Mann-Whitney U.

The results showed that ferritin level in %52.5 of patients was ≥ 3000 ng/ml. Moreover, %87.5 of the patients had normal T4 levels (0.8 to 2 deciliters). Among all patients, subclinical hypothyroidism was the common thyroid dysfunction (%20). Moreover, the most common thyroid dysfunction in patients with normal ferritin levels (≥ 3000 ng/ml) was subclinical hypothyroidism (P = 0.039). Also, the prevalence of hypothyroidism was found to be associated with different age groups (p = 0.036).

It seems that subclinical hypothyroidism is the most common thyroid dysfunction in patients with beta-thalassemia major. The early detection and treatment of patients could improve their quality of life.

To Report a case of bilateral choroidal neovascularization (CNV) and angioid streaks in a patient with b thalassemia.

A 41-year-old male, a known case of b-thalassemia, presented with the gradual decrease of vision from 3 months ago. The best corrected visual acuity was 8/10 in right and 3/10 in the left eye and Marcus Gunn was negative. In slit lamp examination, the anterior segment of both eyes was normal and in the posterior segment of both eyes, dark brown to red irregular bands radiating a few millimeters from a peripapillary ring was visible. There was an active CNV in the right eye and a CNV scar in the left eye. Intravitreal injection of bevacizumab was performed for the right eye.

Angioid Streaks can occur in patients with β thalassemia and one of the complications of angioid streaks is choroidal neovascularization, which can decrease vision.

Among the factors that may be associated with the re-expression gamma-globin in adults is the methylation pattern of the promoter region. The study aimed to determine the association between promoter methylation pattern of the gamma-globin gene in the carriers and affected beta-thalassemia individuals and its expression levels.

This study has been done as a case control- study. After taking blood samples from 30 patients and beta-thalassemia carriers and affected patients with fetal hemoglobin elevated as well as 30 normal individuals, genomic DNA was extracted. Six CpG sites of the promoter region and exon1 of the gamma-globin gene were analyzed by the bisulfite sequencing analysis method. Statistical analysis was carried out using a t-test. The values of p ≤ 0.05 were considered significant for comparing two studied groups. Data were analyzed using SPSS version 16 software.

In this study, hypomethylation of the gamma-globin promoter region in the patients and carriers compared to showed a significant differences in three CpG sites +6, -53 and -162, respectively (p<0.05). In addition, in three cases, CpG site in position -162 was semi methylated; this situation was markedly different from other samples of the patients and normal cases.

Hypomethylation of the gamma-globin gene promoter probably has an auxiliary role in fetal hemoglobin increase.

Accumulation of iron is the most common consequences of repeated blood transfusions in β-thalassemia major patients. Iron chelating effects of alpha-lipoic acid have been reported by several studies. The aim of this study was to investigate effects of supplementation with alpha-lipoic acid, as a chelator, on serum iron and hematological indices in these patients.

Twenty-two β-thalassemia major patients were selected to receive 600 mg alpha-lipoic acid or placebo capsules for 8 w. After a 3-week washout period, order of intervention was replaced as patients who previously received placebo were administered the supplement vise versa for another 8 w. At the end of the study, changes in serum iron, total iron binding capacity and hematological parameters between the treatments were assessed.

Serum concentrations of iron and total iron binding capacity and hematological parameters did not change within the supplementation (p > 0.05). Changes in iron, total iron binding capacity and hematological indices were not significantly different between the two interventions (p > 0.05). White blood cell counts in placebo use increased significantly in males (p = 0.04). The mean corpuscular hemoglobin in placebo patients decreased significantly in all patients and males (p = 0.02 for both).

Results of this study revealed that alpha-lipoic acid supplementation included no beneficial effects on iron, total iron binding capacity and hematological indices in β-thalassemia major patients. Further studies with more participants and longer times are indispensable.

Thalassemia is a group of inherited hemoglobin disorders with defect in the synthesis of hemoglobin chains. 

Case:

The young couple resident in Bandar Abbas,  a 23 year old woman with MCV:63fl; MCH:19; HbA2:3.9  and  a 25 year old man with MCV:94fl; MCH:32; HbA2:2.1; HbF:36, were referred to the Bandar Abbas Medical Genetic & PND Center for genetic counselling before marriage. 

Conclusions:  

A rare CD139 mutation (AAT → GAT) was detected which led to substitution of Asparagine by Aspartic Acid in 139th amino acid in hemoglobin chain and created a hemoglobin variant named Hb Geelong. This is the first report for Hb-Geelong in Iran. It seems that this mutation affects the hemoglobin stability though a non-pathologic process and has a phenotype similar to minor β+ thalassemia.

Understanding the general health status of thalassemia patients and their families can be useful in establishing a better therapeutic relationship with them and thus improve the follow-up and treatment of these patients. This study aimed to determine the correlation between the general health status of patients with beta-thalassemia major and demographic characteristics in Tehran province in 2018.

This is a descriptive correlational study that was conducted in 1397 in Tehran province. The study population consisted of all major thalassemia patients referred to Tehran Special Disease Center, and 147 were enrolled in the study. The “28-item General Health Questionnaire” consisted of 28 items with four domains of physical symptoms, anxiety, social dysfunction, and depression. The content validity and test-retest were measured. Data were analyzed by SPSS 18.

The prevalence of general health disorders was 51.7%. According to the subscales of the questionnaire, 4.1% of patients were suspected of having physical symptoms, 23.8% were suspected of anxiety and insomnia, 8.2% were suspected of social dysfunction, and 16.3% were suspected of depression.

According to the results of this study, patients with thalassemia are exposed to various disorders. Therefore, providing educational programs to alleviate these disorders, provide support to those around them and their families, as well as the presence of a psychologist and psychiatrist alongside these patients.

Beta-thalassemia major is a genetic disorder with known globin defect that leads to chronic hemolytic anemia. Due to the need for recurrent blood transfusion, the risk of infectious diseases such as hepatitis is higher in these patients.

This cross-sectional study recruited 518 patients with thalassemia major in Amirkola Thalassemia Center, 2013-2014 who were selected via census sampling. Patients' blood samples were analyzed for HBsAb, HBsAg, and HCVAb by ELISA test. Data were analyzed in
SPSS V22.

The patients included 268 (51.7%) females and 250 (48.3%) males with the mean age of 27.93±9.88 years. The study showed that 5.79% of patients with thalassemia major were infected with HCV, including 11 (4.4%) males and 19 (7.1%) females and only one male patient was found to be HBsAg positive.

The study showed lower incidence of hepatitis C compared to previous reports from Amirkola Thalassemia Center. In current study the prevalence of HBsAg was also found to be low.

The relationship between iron status and risk of atherosclerosis in beta- thalassemia patients has been shown previously. The aim of this case-control study is to compare common carotid artery intima-media thickness (CIMT) in beta-thalassemia major, intermedia, and minor with healthy individuals.

In this, case-control study, 27 beta-thalassemia major patients, 27 beta-thalassemia intermedia, and 27 beta-thalassemia minor (age: 18-29 years) with similar sex ratio were investigated in Jahrom, Fars province, Southern Iran. In addition, 27 sex-matched healthy controls with the same age range were randomly selected from individuals referred to the out-patient clinic. Exclusion criteria were diabetes, hypertension, obesity, thyroid dysfunction and smoking.

Serum low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were significantly lower in patients with beta-thalassemia major and intermedia in comparison with beta-thalassemia minor and healthy control (P<0.001). In all thalassemia groups CIMT were significantly higher in comparison with healthy individuals (P<0.001). These results were similar after removal of confounding effect of other variables including serum ferritin levels, cholesterol, LDL, HDL, and age.

It seems regardless of other relative risk factors of atherosclerosis, being beta-thalassemia is an influential determinant on the occurrence of atherosclerosis. Maybe some molecular and genetic factors can influence the occurrence of atherosclerosis in these patients that needs further larger combined clinical and basic studies.