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.

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 Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload

2006 ◽  
Vol 124 (2) ◽  
pp. 55-60 ◽  
Author(s):  
Rodolfo Delfini Cançado ◽  
Aline Cristiane de Oliveira Guglielmi ◽  
Carmen Silvia Vieitas Vergueiro ◽  
Ernani Geraldo Rolim ◽  
Maria Stella Figueiredo ◽  
...  
Keyword(s):  
Iron Overload ◽  
Binding Capacity ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Hfe Gene ◽  
Outpatient Unit ◽  
Laboratory Variables ◽  
Hfe Gene Mutations ◽  
Hfe Mutations ◽  
Iron Binding Capacity

CONTEXT AND OBJECTIVE: Hemochromatosis is a common inherited disorder of iron metabolism and one of the most important causes of iron overload. The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with clinical and laboratory variables. DESIGN AND SETTING: Prospective study, in Discipline of Hematology and Oncology, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. METHODS: We studied 35 patients with iron overload seen at our outpatient unit between January 2001 and December 2003. Fasting levels of serum iron and ferritin, and total iron-binding capacity, were assayed using standard techniques. Determinations of C282Y, H63D and S65C mutations in the HFE gene and of HLA-A alleles were performed by polymerase chain reaction (PCR). RESULTS: Twenty-six out of 35 patients (74%) presented at least one of the HFE gene mutations analyzed. Among these, five (14%) were C282Y/C282Y, four (11%) C282Y/H63D, one (3%) H63D/H63D, six (17%) C282Y/WT and ten (29%) H63D/WT. No patients had the S65C mutation and nine (25%) did not present any of the three HFE mutations. Four out of five patients with C282Y/C282Y genotype (80%) and three out of four patients with C282Y/H63D genotype (75%) were HLA A*03. CONCLUSION: Analysis of HFE gene mutations constitutes an important procedure in identifying patients with hereditary hemochromatosis, particularly for patients with iron overload.

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.

Hepcidin, a candidate modifier of the hemochromatosis phenotype in mice

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2841-2843 ◽  
Author(s):  
Gaël Nicolas ◽  
Nancy C. Andrews ◽  
Axel Kahn ◽  
Sophie Vaulont
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Genetic Modifier ◽  
Hereditary Hemochromatosis ◽  
Iron Accumulation ◽  
Hfe Gene ◽  
Type I ◽  
Regulatory Peptide ◽  
Liver Iron ◽  
Very High

Abstract Hereditary hemochromatosis (HH) type I is a disorder of iron metabolism caused by a mutation in the HFE gene. Whereas the prevalence of the mutation is very high, its penetrance seems very low. The goal of our study was to determine whether hepcidin, a recently identified iron-regulatory peptide, could be a genetic modifier contributing to the HH phenotype. In mice, deficiency of either HFE (Hfe-/-) or hepcidin (Usf2-/-) is associated with the same pattern of iron overload observed in patients with HH. We intercrossed Hfe-/- and Usf2+/- mice and asked whether hepcidin deficiency increased the iron burden in Hfe-/- mice. Our results showed that, indeed, liver iron accumulation was greater in the Hfe-/-Usf2+/- mice than in mice lacking Hfe alone. This result, in agreement with recent findings in humans, provides a genetic explanation for some variability of the HH phenotype. (Blood. 2004;103: 2841-2843)

scholarly journals Hfe Gene Knock-Out in a Mouse Model of Hereditary Hemochromatosis Affects Bodily Iron Isotope Compositions

2021 ◽  
Vol 8 ◽  
Author(s):  
Emmanuelle Albalat ◽  
Thibault Cavey ◽  
Patricia Leroyer ◽  
Martine Ropert ◽  
Vincent Balter ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Whole Blood ◽  
Isotope Composition ◽  
Hereditary Hemochromatosis ◽  
Iron Concentration ◽  
Hfe Gene ◽  
Iron Isotope ◽  
Heavy Isotope ◽  
Knock Out

Hereditary hemochromatosis is a genetic iron overload disease related to a mutation within the HFE gene that controls the expression of hepcidin, the master regulator of systemic iron metabolism. The natural stable iron isotope composition in whole blood of control subjects is different from that of hemochromatosis patients and is sensitive to the amount of total iron removed by the phlebotomy treatment. The use of stable isotopes to unravel the pathological mechanisms of iron overload diseases is promising but hampered by the lack of data in organs involved in the iron metabolism. Here, we use Hfe−/− mice, a model of hereditary hemochromatosis, to study the impact of the knock-out on iron isotope compositions of erythrocytes, spleen and liver. Iron concentration increases in liver and red blood cells of Hfe−/− mice compared to controls. The iron stable isotope composition also increases in liver and erythrocytes, consistent with a preferential accumulation of iron heavy isotopes in Hfe−/− mice. In contrast, no difference in the iron concentration nor isotope composition is observed in spleen of Hfe−/− and control mice. Our results in mice suggest that the observed increase of whole blood isotope composition in hemochromatosis human patients does not originate from, but is aggravated by, bloodletting. The subsequent rapid increase of whole blood iron isotope composition of treated hemochromatosis patients is rather due to the release of hepatic heavy isotope-enriched iron than augmented iron dietary absorption. Further research is required to uncover the iron light isotope component that needs to balance the accumulation of hepatic iron heavy isotope, and to better understand the iron isotope fractionation associated to metabolism dysregulation during hereditary hemochromatosis.

Dysmetabolic iron overload syndrome and its relationship with HFE gene mutations and with liver steatosis

2020 ◽  
Vol 52 (6) ◽  
pp. 683-685
Author(s):  
Agustín Castiella ◽  
Iratxe Urreta ◽  
Eva Zapata ◽  
MªDolores de Juan ◽  
José Mª Alústiza ◽  
...  
Keyword(s):  
Iron Overload ◽  
Liver Steatosis ◽  
Gene Mutations ◽  
Hfe Gene ◽  
Hfe Gene Mutations

scholarly journals Iron age: novel targets for iron overload

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 216-221 ◽  
Author(s):  
Carla Casu ◽  
Stefano Rivella
Keyword(s):  
Iron Overload ◽  
Iron Age ◽  
Iron Metabolism ◽  
Iron Absorption ◽  
Hereditary Hemochromatosis ◽  
Therapeutic Approaches ◽  
Hepcidin Expression ◽  
Beneficial Effects ◽  
Excess Iron ◽  
Major Factors

Abstract Excess iron deposition in vital organs is the main cause of morbidity and mortality in patients affected by β-thalassemia and hereditary hemochromatosis. In both disorders, inappropriately low levels of the liver hormone hepcidin are responsible for the increased iron absorption, leading to toxic iron accumulation in many organs. Several studies have shown that targeting iron absorption could be beneficial in reducing or preventing iron overload in these 2 disorders, with promising preclinical data. New approaches target Tmprss6, the main suppressor of hepcidin expression, or use minihepcidins, small peptide hepcidin agonists. Additional strategies in β-thalassemia are showing beneficial effects in ameliorating ineffective erythropoiesis and anemia. Due to the suppressive nature of the erythropoiesis on hepcidin expression, these approaches are also showing beneficial effects on iron metabolism. The goal of this review is to discuss the major factors controlling iron metabolism and erythropoiesis and to discuss potential novel therapeutic approaches to reduce or prevent iron overload in these 2 disorders and ameliorate anemia in β-thalassemia.

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