scholarly journals Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

2021 ◽  
Vol 8 (4) ◽  
pp. 233-247
Author(s):  
Bhuvana Selvaraj ◽  
◽  
Sangeetha Soundararajan ◽  
Shettu Narayanasamy ◽  
Ganesan Subramanian ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Globin Gene ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Beta Thalassemia ◽  
Hemochromatosis Gene

<abstract> <p>Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with <italic>HFE</italic> gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of <italic>HFE</italic> variants among beta thalassemia cases and their effect on iron overload. The frequency of three <italic>HFE</italic> variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating <italic>HFE</italic> variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C <italic>HFE</italic> variant was absent in the present study. Iron overload was completely absent in the control cases among all three <italic>HFE</italic> genotypes. Hence it is inferred from the present investigation, analysis of <italic>HFE</italic> genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.</p> </abstract>

scholarly journals Dysmetabolic Hyperferritinemia: All Iron Overload Is Not Hemochromatosis

2015 ◽  
Vol 9 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Jasbir Makker ◽  
Ahmad Hanif ◽  
Bharat Bajantri ◽  
Sridhar Chilimuri
Keyword(s):  
Iron Overload ◽  
Autosomal Recessive ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Autosomal Recessive Disorder ◽  
Organ Damage ◽  
High Serum ◽  
Hemochromatosis Gene ◽  
Secondary Iron Overload ◽  
Iron Binding Capacity

Disturbances in iron metabolism can be genetic or acquired and accordingly manifest as primary or secondary iron overload state. Organ damage may result from iron overload and manifest clinically as cirrhosis, diabetes mellitus, arthritis, endocrine abnormalities and cardiomyopathy. Hemochromatosis inherited as an autosomal recessive disorder is the most common genetic iron overload disorder. Expert societies recommend screening of asymptomatic and symptomatic individuals with hemochromatosis by obtaining transferrin saturation (calculated as serum iron/total iron binding capacity × 100). Further testing for the hemochromatosis gene is recommended if transferrin saturation is >45% with or without hyperferritinemia. However, management of individuals with low or normal transferrin saturation is not clear. In patients with features of iron overload and high serum ferritin levels, low or normal transferrin saturation should alert the physician to other - primary as well as secondary - causes of iron overload besides hemochromatosis. We present here a possible approach to patients with hyperferritinemia but normal transferrin saturation.

scholarly journals Hemochromatosis: one form of iron-overload diseases

2013 ◽  
Vol 154 (29) ◽  
pp. 1156-1164 ◽  
Author(s):  
Ferenc Szalay
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Clinical Symptoms ◽  
Fetal Liver ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Organ Injury ◽  
Beta Thalassemia ◽  
Hfe Gene ◽  
Kinase Gene

Iron-overload diseases are typically insidious, causing progressive and irreversible organ injury before clinical symptoms develop. Some iron-overload diseases as HFE-associated hemochromatosis and beta-thalassemia are quite common, whereas others are very rare. Early diagnosis is important since iron toxicity can be attenuated or prevented. Significant progress of our knowledge on iron metabolism developed in the past years. We learned a lot about HFE gene mutations, function of ferroportin and hepcidin, the hypoferremia hormone produced by the liver. However, many questions are still open. Special forms of localized iron overload are the Hallervorden-Spatz syndrome and pantothenate kinase gene mutation associated neurodegeneration causing progressive extrapyramidal movement disorders. Neonatal hemochromatosis is a severe systemic iron-overload disorder due to gestational alloimmune liver disease caused by transplacental maternal IgG directed against the fetal liver. This review article gives an overview on iron metabolism and iron-overload disease. Pathomechanism, diagnosis and treatment of hereditary hemochromatosis are discussed. Orv. Hetil., 2013, 154, 1156–1164.

Investigation of beta globin gene mutations in Syrian refugee patients with thalassemia major

2019 ◽  
Vol 44 (2) ◽  
pp. 126-129
Author(s):  
Hatice Çevirici ◽  
Can Acıpayam ◽  
Ebru Dündar Yenilmez ◽  
Fatma Burcu Belen ◽  
Esra Pekpak ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Amplification Refractory Mutation System ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Thalassemia Major ◽  
Mutation System

Abstract Objectives This study, detection of beta globin gene mutations in thalassemia major patients who migrated from Syria to Kahramanmaraş region were planned. Materials and methods The study included 35 Syrian national beta thalassemia major patients. Beta globin gene mutations were detected by ARMS (Amplification Refractory Mutation System) method, RFLP (Restriction Fragment Length Polymorphism) method and DNA sequence analysis. Codon 15, codon 9/10, codon 5 and codon 8 mutations, which we could not detect with other methods in our study, were detected by sequence analysis. Results In beta thalassemia major patients, 16 types of mutations were detected, the most common being IVS-I-110 (n=8). Other mutations are according to frequency order IVS-II-745 (n=3), codon 44 (n=3), codon 15 (n=3), IVS-I-110/IVS-I-1 (n=3), codon 5 (n=2), IVS-I-1 (n=2), codon 8/IVS-II-1 (n=2), codon 44/codon 15 (n=2), IVS-II-1 (n=1), codon 39 (n=1), IVS-I-6/codon 5 (n=1), codon 9/10 (n=1), IVS-I-110/codon 39 (n=1), IVS-I-5/IVS-II-1 (n=1), codon 39/IVS-II-745 (n=1). Conclusions According to the results of our study beta-thalassemia mutations in Syrian immigrant groups show heterogeneity and mutation types of mutation map is similar to Turkey. The conclusion is to prevent families to have a second patient child by genetic counseling.

scholarly journals Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey

2011 ◽  
Vol 2011 (4) ◽  
pp. 264-268 ◽  
Author(s):  
Ali Aycicek ◽  
Ahmet Koc ◽  
Zeynep Canan Ozdemir ◽  
Hasan Bilinc ◽  
Abdurrahim Kocyigit ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Thalassemia Major

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

2016 ◽  
Vol 4 (2) ◽  
pp. 226-231 ◽  
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.

scholarly journals Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

2019 ◽  
Author(s):  
Hasan Smesam ◽  
Hasan Qazmooz ◽  
Sareh Arjmand ◽  
Hussein Kadhem Al-Hakeim ◽  
Seyed Omid Ranaei‐Siadat,
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Iron Chelation ◽  
Fold Increase ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Control Group ◽  
Beta Globin ◽  
Beta Thalassemia Major ◽  
Globin Chains

Beta thalassemia major (&beta;-TM) disorder characterized by the lack, or severe reduction in the production of hemoglobin &beta;-globin chains. The standard protocol for the management of &beta;-TM is blood transfusion and iron chelation therapy to reduce the iron overload state. The present study aimed to investigate the relationships between two iron regulatory hormones, hepcidin (HEPC) and erythroferrone (ERFE) levels and iron status parameters (ISPs) in Iraqi patients with &beta;-TM. ISPs and hormones were measured in sixty patients and compared with thirty healthy controls. The results indicated significant changes in different iron status parameters, while ferritin (FRT) with the ~11 fold increase showed the most change. Significant reduction in HEPC and increase in ERFE levels were detected in patients as compared to the control group, while no direct correlation was identified with the other measured ISPs. Receiver operating characteristic (ROC) analysis showed that the z-score of the composite of ERFE+FRT has a full diagnostic ability for &beta;-TM. In conclusion, our finding indicated the correlation between different ISPs, FRT as the leading predictor of iron overload and tow main iron regulatory hormones.

scholarly journals Major Depression in Children with β-Thalassemia Major is Strongly Associated with the Number of Blood Transfusions, Iron Overload and Increased Levels of Interleukin-1β

2019 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Asawer Hassan Najm ◽  
Arafat Hussein Al-Aldujaili ◽  
Michael Maes
Keyword(s):  
Iron Overload ◽  
Inflammatory Responses ◽  
Iron Status ◽  
Thalassemia Major ◽  
Treatment Modalities ◽  
Beta Thalassemia ◽  
Blood Transfusions ◽  
Healthy Children ◽  
Beta Thalassemia Major ◽  
Increased Risk

Beta-thalassemia major (&beta;-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with &beta;-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with &beta;-TM. The Children&rsquo;s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1&beta;, IL-10, and TNF-&alpha; were measured in &beta;-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in &beta;-TM is associated with a greater number of blood transfusions, increased IO and IL-1&beta; levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1&beta; and TNF-&alpha;. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in &beta;-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with &beta;-TM undergoing blood transfusions.

scholarly journals Cytokine Dependent Hematopoietic Cell Linker (CLNK) is Highly Elevated in Blood Transfusion Dependent Beta-Thalassemia Major Patients

2019 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Hawraa Hussein Al-Mayali ◽  
Michael Maes
Keyword(s):  
Iron Status ◽  
Globin Gene ◽  
Adaptor Protein ◽  
Thalassemia Major ◽  
Severe Form ◽  
Hematopoietic Cell ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Beta Thalassemia Major ◽  
Globin Chains

Beta-thalassemia major (&beta;-TM) is a severe form of thalassemia caused by mutations in the &beta;-globin gene, resulting in partial or complete deficiency of &beta;-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine dependent hematopoietic cell linker (CLNK) belongs to the adaptor protein family and has the capacity to interact with multiple signaling proteins thereby modulating signal transduction. The aim of the present study was to examine CLNK in sera of &beta;-TM patients and examine its association with iron overload biomarkers. Sixty &beta;-TM patients, aged 3&ndash;12 years old and undergoing blood transfusions, and 30 healthy control children were recruited and CLNK, ferritin and iron status parameters were measured. The results showed a significant increase (p &lt; 0.001) in serum CLNK levels in &beta;-TM patients as compared with normal controls. The increased levels of CLNK were significantly associated with increased ferritin levels. Increased CLNK levels in &beta;-TM may be explained by reciprocal effects between immune signaling and immature erythrocytes, which, release soluble receptors and signaling molecules, including CLNK, in the blood.

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