Investigation of correlation between H63D and C282Y mutations in HFE gene and serum Ferritin level in beta-thalassemia major patients

Background: Beta-Thalassemia is a genetic disorder which is associated with a lot of complications. Frequent blood transfusions result in increased iron deposition in various tissues leading to dysfunction of many vital organs. Endocrine disorders constitute a major part of such complications increasing the morbidity of thalassemia manifold in the affected patients. Methods: This is a descriptive cross sectional study carried out in 100 diagnosed patients of beta- thalassemia major who had visited the OPD/IPD of Subharti Medical College & affiliated Hospitals, Meerut for routine blood transfusion or for any other complication. Patients were clinically examined and investigated for presence of one or more endocrine disorders on their routine appointments. Results: Endocrine disorders were detected in a total of 82 patients. Diabetes mellitus was detected in 12% patients, hypothyroidism in 36% patients and delayed puberty was found in 72% patients. Mean serum ferritin level was found to be 5831.0±2860.5 ng/ml in beta-thalassemia Major patients, while it was in normal range in control subjects. Conclusion: Research concluded with finding of Delayed puberty (72%), Hypothyroidism (36%) and diabetes mellitus as (12%) in beta thalassemia patients who were on regular blood transfusion therapy. Iron overload as serum ferritin level was found to be highly raised in all study case. On the basis of our study we recommend that early detection and management protocols for these endocrinopathies may improve the life prospects of beta-thalassemia Major patients. Keywords: Endocrine disorders, Hypothyroidism, Delayed puberty, Diabetes Mellitus Serum ferritin, Thalassemia Major.

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BETA THALASSEMIA MAJOR;

The Professional Medical Journal ◽

10.29309/tpmj/2017.24.02.521 ◽

2017 ◽

Vol 24 (02) ◽

pp. 315-321

Author(s):

Asma Mehreen ◽

Saeeda Bano ◽

Bushra Ujala

Keyword(s):

Serum Ferritin ◽

Serum Ferritin Level ◽

Controlled Trial ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Baseline Serum ◽

Beta Thalassemia Major ◽

Group A ◽

Group B

Introduction: β-Thalassemia major (β-TM) is a genetic haemoglobin disorderwhich is relatively common in some geographical areas. β-TM is characterized by severe anaemia,which needs a continuous blood transfusion regimen starting from the first months of life toprolong survival. Objectives: To compare mean reduction in serum ferritin level with deferasiroxand desferrioxamine when used as an iron chelator in multi-transfused beta thalassemia major.Study design: Randomized controlled trial. Setting: Thalassemia clinic, The Children’s Hospitaland The Institute of Child Health, Lahore. Duration of Study with Dates: Study was carried outover a period of nine months from 28-06-2015 to 27-03-2016. Subjects and Methods: A totalof 100 patients (50 patients in each group). The patients were randomly allocated into twogroups using random numbers stable. Group-A received Deferasirox and group-B receivedDesferrioxamine. Results: Mean age of the patients was 7.42±4.13 and 7.87±4.13 in group-Aand B, respectively. Regarding sex distribution, 26 patients (52.0%) in group-A and 28 patients(56.0%) in group-B were male while 24 patients (48.0%) in group-A and 22 patients (44.0%) ingroup-B were female. Reduction from baseline in group-A was 783.60±413.66 ng/ml and ingroup-B 552.80±155.45 ng/ml (P<0.001) There was more reduction in group-A. In group-Abaseline serum ferritin level was 2495.00±1259.10 ng/ml and at 9 month 1712.00±1019.36 ng/ml (P<0.001). Similarly in group-B baseline serum ferritin level was 2422.80±910.43 ng/ml andat 9 month 1883±862.72 ng/ml (P<0.001). Conclusion: In conclusion, deferasirox was moreeffective in terms of reduction in serum ferritin level when compared with desferrioxamine inmulti-transfused beta thalassemia major patients.

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Association of Body mass index and serum ferritin level in pediatrics with Beta-thalassemia major disease

Iranian Journal of Pediatric Hematology & Oncology ◽

10.18502/ijpho.v12i1.8359 ◽

2022 ◽

Author(s):

Saeed Yousefian ◽

Ghassem Miri Aliabad ◽

Rana Saleh ◽

Majid Khedmati

Keyword(s):

Body Mass Index ◽

Blood Transfusion ◽

Body Mass ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Major Disease ◽

Beta Thalassemia Major

Background: Beta-thalassemia major is a type of inherited blood disease that results in variable outcomes such as severe anemia due to haemoglobin chains. Recurrent and lifelong blood transfusions as a treatment in beta-thalassemia major disease lead to iron deposition in various organs and cause the failure of multiple organs. Failure of affected organs leads to Body mass index (BMI) abnormality. This study aimed to evaluate the association between BMI and serum ferritin level as a marker for iron overload. Materials and Methods: A cross-sectional study designed and conducted with total number of 740 paediatrics, with mean age about 14.2±8.7 years old and with beta-thalassemia major requiring recurrent blood transfusion. Patient information, including demographics, serum ferritin level and percentage of BMI, was recorded and analysed by SPSS 25.0 and the statistical significant level, considered as 0.05. Results: A total number of 740 paediatrics with beta-thalassemia major disease (mean age about 14.2±8.7 years) were included to study to examine the association between serum ferritin level and their BMI. The total mean serum level of ferritin calculated about 3326 ± 3859 Nanogram/mililitter (ng/ml). Totally, 447 (60.4%) case of them had BMI percentile less than 5%, 274 (37.02%), 16 (2.16%) and 3 (0.4%) had BMI percentile 5%-85%, 85%-95% and more than 95%. There was no relation between gender and serum ferritin levels. The relationship between age and BMI has been positive (P=0.002). Finally, it resulted that there was a negative relationship between the BMI percentile and mean serum ferritin levels in paediatrics with beta-thalassemia major (P=0.031). Conclusion: Frequent Blood transfusion is associated with elevated serum ferritin level in paediatrics with beta-thalassemia major disease and experiencing lower percentiles of BMI in these patients.

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Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1392 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Alaa Mutter Jabur Al-Shibany ◽

AalanHadi AL-Zamili

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Iron Level ◽

The Mean ◽

T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

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Left ventricular dysfunction in transfusion dependent beta Thalassemia major patients in Bangladesh

Cardiovascular Journal ◽

10.3329/cardio.v9i1.29539 ◽

2016 ◽

Vol 9 (1) ◽

pp. 31-35

Author(s):

Simu Saha ◽

Tapash Saha ◽

AKM Amirul Morshed ◽

Md Lutful Ehsan Fatmi ◽

Nazneen Umme Zakia ◽

...

Keyword(s):

Diastolic Dysfunction ◽

Serum Ferritin ◽

Cardiac Dysfunction ◽

Serum Ferritin Level ◽

Ventricular Dysfunction ◽

Early Stage ◽

Ferritin Level ◽

Thalassemia Major ◽

Left Ventricular ◽

Beta Thalassemia

Background: Thalassemia major is an inherited haemoglobin disorder resulting in chronic haemolytic anaemia. Patients with beta thalassemia major are maintained on continuous blood transfusion regimens resulting in iron overload that adversely affects both the structure and function of the heart and other vital organs which can be easily prevented with iron chelating therapy. The aim of the study was to detect left ventricular dysfunction at an early stage so that early effective intervention can be done.Methods: A total of 50 patients with beta thalassemia were included in the study by non randomized qualitative purposive sampling from July 2013 to June 2014. Their total body iron status was be assessed by doing serum ferritin level. Left ventricular systolic and diastolic function was assessed by echocardiographyResults: Cardiac dysfunction was present in 11 patients with high incidence in patients with low pre-transfusional haemoglobin group (p=0.4) and in patients having high serum ferritin level (p=0.02). Systolic cardiac dysfunction was present in 7(14%) of patients and diastolic dysfunction was present in 4(8%) of patients. There was a weak but significant correlation between left ventricular ejection fraction and serum ferritin concentration (r=-0.22; p=0.03). Only few (8%) patients had diastolic dysfunction.Conclusion: Patients with beta thalassaemia on an adequate transfusion showed an abnormal left ventricular systolic function. In early stage of disease diastolic function was normal but after repeated transfusion there were impaired relaxation indicating diastolic dysfunction. These findings seem mainly to be related to chronic anaemia and serum ferritin levelCardiovasc. j. 2016; 9(1): 31-35

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Thyroid Function Status and Echocardiography Abnormalities in Patients with Beta Thalassemia Major in Bahrain

Clinical Medicine Insights Cardiology ◽

10.4137/cmc.s10702 ◽

2013 ◽

Vol 7 ◽

pp. CMC.S10702 ◽

Cited By ~ 1

Author(s):

Taysir S. Garadah ◽

Najat A. Mahdi ◽

Ahmed M. Jaradat ◽

Zuheir A. Hasan ◽

Das S. Nagalla

Keyword(s):

Regression Analysis ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Systolic Function ◽

Ferritin Level ◽

Thalassemia Major ◽

Tissue Doppler ◽

Thyroid Stimulating Hormone ◽

Beta Thalassemia ◽

Pulsed Doppler

Background Thyroid gland dysfunction and echocardiographic cardiac abnormalities are well-documented in patients with transfusion dependent beta-thalassemia major (β-TM). Aim This cross-sectional analytic study was conducted to investigate left ventricle (LV) diastolic and systolic function using pulsed Doppler (PD) and tissue Doppler (TD) echocardiography and correlate that with serum level thyroid stimulating hormone in patients with β-TM. Methods The study was conducted on patients with β-TM (n = 110, age 15.9 ± 8.9 years) and compared with a control group (n = 109, age 15.8 ± 8.9 years). In all participants, echocardiographic indices of PD and TD were performed and blood samples were withdrawn for measuring the serum level of TSH, free T4, and ferritin. A linear regression analysis was performed on TSH level as the dependent variable and serum ferritin as independent. Stepwise multiple regression analysis was used to determine the odds ratio of different biochemical and echo variables on the risk of developing hypothyroidism. Results Patients with β-TM compared with controls had thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm/M2, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm/m2, P < 0.01) and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm/m2, P < 0.001). In addition, β-TM patients had higher transmitral E wave velocity (E) (70.81 ± 10.13 vs. 57.53 ± 10.13 cm/s, P = 0.02) and E/A ratio (1.54 ± 0.18 vs. 1.23 ± 0.17, P < 0.01) and shorter deceleration time (DT) (170.53 ± 13.3 vs. 210.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in the β-TM group (19.68 ± 2.81 vs. 13.86 ± 1.41, P < 0.05). The tissue Doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in the β-TM group compared with controls with Sm, 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05 and (Em), 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec. P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls 2.85 ± 0.56 vs. 1.743 ± 0.47 m sec, respectively, P < 0.01). The prevalence of subclinical hypothyroidism in patients with β-TM was 15.4%, with significantly higher mean serum TSH compared with controls (6.78 ± 1.5 vs. 3.10 ± 1.02 μIU/mL, P < 0.01) and positively correlated with the serum ferritin level ( r = 0.34, P = 0.014). On multiple regression analysis, the LV mass, LVEF%, and E/A ratio were not positive predictors of hypothyroidism in patients with β-TM. Conclusion We conclude that patients with β-TM had a high prevalence of subclinical hypothyroidism of 15.4%. Thyroid stimulating hormone was significantly high and positively correlated with the serum ferritin level. Echo cardiographic pulsed Doppler showed a restrictive LV diastolic pattern suggestive of severe diastolic dysfunction with preserved left ventricle systolic function.

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Iron chelation therapy needed for serum ferritin overloaded patients of beta thalassemia major

Thalassemia Reports ◽

10.4081/thal.2021.9779 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wasim Muhammad ◽

Muhammad Ishaq ◽

Muhammad J. Khan ◽

Umair Ahmad ◽

Muhammad Waseem

Keyword(s):

Serum Ferritin ◽

Ferritin Level ◽

Iron Chelation ◽

Care Facility ◽

Health Care Facility ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Cross Sectional ◽

Beta Thalassemia Major ◽

Khyber Pakhtunkhwa Province

The main objective of the current study is to evaluate the level and overload of serum ferritin in multi-transfused beta Thalassemia major patients. There is an earnest need to defend the chelation treatment and to make mindfulness about the results of serum ferritin in the patients beta Thalassemia major. This is a Cross sectional analytical study performed in Fatimid foundation Hayatabad, Peshawar, Khyber Pakhtunkhwa province of Pakistan. Those patients who has beta thalassemia major are included in this study. In this study there are total 108 patients in which 54 males and 54 females. The highest mean of serum ferritin level in the category of male was in the age of 12 years were finds 8160.5 ng/mL. Among the female the highest mean of ferritin level was in the age of 17 years were finds 13,349.5 ng/mL. In this study majority of patient’s revealed much high levels of serum ferritin. These levels reveal insufficient chelation. Appropriate chelation of iron load can improve the quality of the life of these patients. The low level of education, Poverty problems, and insufficient health care facility of are the main obstacle in the effective management of ferritin overload in thalassemia patients.

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Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2016.055 ◽

2016 ◽

Vol 4 (2) ◽

pp. 226-231 ◽

Cited By ~ 7

Author(s):

Azza Aboul Enein ◽

Nermine A. El Dessouky ◽

Khalda S. Mohamed ◽

Shahira K. A. Botros ◽

Mona F. Abd El Gawad ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Iron ◽

Gene Mutations ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Hfe Gene ◽

Carrier Status ◽

Beta Thalassemia Major ◽

Hfe Gene Mutations

AIM: This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status. SUBJECTS AND METHODS: The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing.RESULTS: Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001).CONCLUSION: Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients.

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Thyroid profile in patients of thalassemia with multiple blood transfusions and high serum ferritin: a cross-sectional study

Pediatric Review International Journal of Pediatric Research ◽

10.17511/ijpr.2020.i08.02 ◽

2020 ◽

Vol 7 (8) ◽

pp. 401-408

Author(s):

Dr. Rohit Khandelwal ◽

◽

Dr. Muralidhar Gundluru ◽

Dr. Leeni Mehta K. ◽

◽

...

Keyword(s):

Serum Ferritin ◽

Thyroid Dysfunction ◽

Ferritin Level ◽

Thalassemia Major ◽

High Serum ◽

The Body ◽

Beta Thalassemia ◽

Blood Transfusions ◽

Beta Thalassemia Major ◽

Tsh Levels

Introduction: Beta-thalassemia major patients undergo regular blood transfusion resulting ingrowth faltering and various endocrine problems including thyroid dysfunction due to iron overloadin the body. This study was conducted to determine the frequency of thyroid dysfunction in childrenpresenting with Beta-thalassemia major on regular blood transfusions. Materials and methods:Sixty children were included with proven beta-thalassemia major who reported to the Department ofPediatrics, VIMS, and RC, Bangalore. Inclusion criteria: 1.Children 4 to 18 years age group .2.Thechild received transfusions for more than 2 years. 3.Children with serum ferritin level >700.Results: In this study, four patients(6.8%) had overt hypothyroidism, eight patients(13.6%) hadsubclinical hypothyroidism and 47 patients(79.7%) had euthyroid status. There was a positivecorrelation between Ferritin and T4, TSH levels. i.e., with an increase in Ferritin level, there was anincrease in T4, TSH levels, and vice versa. However, the correlation was significant with TSH. Therewas a significant negative correlation between Ferritin and T3 levels. i.e with an increase in Ferritinlevel, there was a decrease in T3 levels and vice versa. Conclusion: Thyroid dysfunction can exist inthalassemia patients on multiple transfusions and chelation therapy with high serum ferritin levels.Detection of hypothyroidism is important as inexpensive oral replacement therapy is readilyavailable. Hence regular screening of beta-thalassemia major patients for Serum T3, Serum T4,Serum TSH for early detection and timely treatment could improve the life expectancy and quality oflife of these patients.

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