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 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 Coincidental nontransfusional iron overload and thalassemia minor: association with HLA-linked hemochromatosis

Blood ◽  
1981 ◽  
Vol 58 (4) ◽  
pp. 844-848 ◽  
Author(s):  
CQ Edwards ◽  
MH Skolnick ◽  
JP Kushner
Keyword(s):  
Iron Overload ◽  
Autosomal Recessive ◽  
Transferrin Saturation ◽  
Young Male ◽  
Autosomal Recessive Disorder ◽  
Beta Thalassemia ◽  
Iron Loading ◽  
Thalassemia Minor ◽  
Hla Haplotypes

A pedigree was studied in which five individuals with beta-thalassemia minor were found to have nontransfusional hemochromatosis. Three were children under the age of 10 and two were young male adults, ages 28 and 33. A 5-yr-old child without evidence of thalassemia also had hemochromatosis. Since hemochromatosis is transmitted as an HLA-linked autosomal recessive disorder, HLA haplotypes serve as markers of hemochromatosis alleles. In this pedigree, five identifiable HLA haplotypes were associated with hemochromatosis alleles. Only individuals with two hemochromatosis alleles (homozygosity) had heavy iron loads, whether beta-thalassemia minor was present or not. Individuals with beta-thalassemia minor but without a hemochromatosis allele had normal transferrin saturation. A 65-yr-old man with beta- thalassemia minor and a single hemochromatosis allele had only a minimally elevated transferrin saturation (54%). The presence of beta- thalassemia minor did not appear to accentuate the degree of iron loading expected in individuals homozygous or heterozygous for hemochromatosis alleles. Our findings suggest that nontransfusional hemochromatosis found in association with beta-thalassemia minor is due primarily to homozygosity for hemochromatosis.

scholarly journals Coincidental nontransfusional iron overload and thalassemia minor: association with HLA-linked hemochromatosis

Blood ◽  
1981 ◽  
Vol 58 (4) ◽  
pp. 844-848 ◽  
Author(s):  
CQ Edwards ◽  
MH Skolnick ◽  
JP Kushner
Keyword(s):  
Iron Overload ◽  
Autosomal Recessive ◽  
Transferrin Saturation ◽  
Young Male ◽  
Autosomal Recessive Disorder ◽  
Beta Thalassemia ◽  
Iron Loading ◽  
Thalassemia Minor ◽  
Hla Haplotypes

Abstract A pedigree was studied in which five individuals with beta-thalassemia minor were found to have nontransfusional hemochromatosis. Three were children under the age of 10 and two were young male adults, ages 28 and 33. A 5-yr-old child without evidence of thalassemia also had hemochromatosis. Since hemochromatosis is transmitted as an HLA-linked autosomal recessive disorder, HLA haplotypes serve as markers of hemochromatosis alleles. In this pedigree, five identifiable HLA haplotypes were associated with hemochromatosis alleles. Only individuals with two hemochromatosis alleles (homozygosity) had heavy iron loads, whether beta-thalassemia minor was present or not. Individuals with beta-thalassemia minor but without a hemochromatosis allele had normal transferrin saturation. A 65-yr-old man with beta- thalassemia minor and a single hemochromatosis allele had only a minimally elevated transferrin saturation (54%). The presence of beta- thalassemia minor did not appear to accentuate the degree of iron loading expected in individuals homozygous or heterozygous for hemochromatosis alleles. Our findings suggest that nontransfusional hemochromatosis found in association with beta-thalassemia minor is due primarily to homozygosity for hemochromatosis.

Iron status of adolescent girls from two boarding schools in southern Benin

2008 ◽  
Vol 11 (7) ◽  
pp. 737-746 ◽  
Author(s):  
Halimatou Alaofè ◽  
John Zee ◽  
Romain Dossa ◽  
Huguette Turgeon O’Brien
Keyword(s):  
Iron Deficiency ◽  
Vitamin C ◽  
Adolescent Girls ◽  
Binding Capacity ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Meat Consumption ◽  
Boarding Schools ◽  
Important Health ◽  
Iron Binding Capacity

AbstractIron deficiency (ID) is the most prevalent micronutrient deficiency in the world, particularly in developing countries. Blood samples and a qualitative FFQ on Fe- and vitamin C-rich foods were obtained in 180 adolescent girls aged 12 to 17 years living in two boarding schools from south Benin. ID, defined as serum ferritin either <20μg/l or 20–50μg/l, plus two of the following parameters: serum Fe<11μmol/l, total iron-binding capacity>73μmol/l or transferrin saturation<20%, was found in 32% of subjects. Anaemia (Hb<120g/l) was found in 51% of adolescents, while 24% suffered from iron-deficiency anaemia (IDA) (ID and Hb<20g/l). After adjusting for confounding factors (age, mother's and father's occupation, household size) in a logistic regression equation, subjects having a low meat consumption (beef, mutton, pork) (<4 times/week) were more than twice as likely to suffer from ID (OR=2·43; 95% CI 1·72, 3·35;P=0·04). Adolescents consuming less fruits (<4 times/week) also had a higher likelihood of suffering from ID (OR=1·53; 95% CI 1·31, 2·80;P=0·03). Finally, subjects whose meat consumption was low were twice as likely to suffer from IDA (OR=2·24; 95% CI 1·01, 4·96;P=0·04). The prevalence of ID represents an important health problem in these Beninese adolescent girls. A higher consumption of Fe-rich foods and of promoters of Fe absorption (meat factor and vitamin C) is recommended to prevent ID deficiency in these subjects.

scholarly journals Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study

2022 ◽  
Author(s):  
Eric P. Skaar ◽  
Roger Echols ◽  
Yuko Matsunaga ◽  
Anju Menon ◽  
Simon Portsmouth
Keyword(s):  
Nosocomial Pneumonia ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Efficacy And Safety ◽  
Baseline Serum ◽  
Post Hoc Analysis ◽  
Iron Binding Capacity ◽  
Post Hoc

AbstractCritically ill patients often present with low serum iron levels or anemia. We evaluated the impact of iron levels and iron homeostasis on the efficacy and safety of cefiderocol, an iron-chelator siderophore cephalosporin, in patients with nosocomial pneumonia in a post hoc analysis of the randomized, double-blind, Phase 3 APEKS-NP study (NCT03032380). Patients with Gram-negative nosocomial pneumonia received cefiderocol 2 g, 3-h infusion, q8h, or high-dose, extended-infusion meropenem 2 g, 3-h infusion, q8h, for 7–14 days. Efficacy and safety parameters, including specific iron homeostasis parameters (i.e., hepcidin, iron, total iron binding capacity, transferrin saturation), were analyzed according to baseline iron levels. In the cefiderocol and meropenem arms, 79.1% (117/148) and 83.3% (125/150) randomized patients, respectively, had low baseline serum iron levels. Rates of 14-day (12.3% [14/114] vs 11.6% [14/121]) and 28-day all-cause mortality (20.5% [23/112] vs 19.0% [23/121]), clinical cure (63.2% [72/114] vs 67.2% [82/122]), and microbiological eradication (43.6% [41/94] vs 48.1% [51/106]) at test of cure were similar in cefiderocol vs meropenem arms, respectively. In the overall safety population, rates of anemia-related adverse events were similar (cefiderocol arm 18.2% [27/148], meropenem arm 18.7% [28/150]). Changes from baseline to test of cure in hepcidin, iron, total iron binding capacity, and transferrin saturation were similar between treatment arms. Cefiderocol treatment did not affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Clinicaltrials.gov registration: NCT03032380. Date of registration: 26 January 2017.

scholarly journals Iron-binding activity in yeast frataxin entails a trade off with stability in the α1/β1 acidic ridge region

2010 ◽  
Vol 426 (2) ◽  
pp. 197-203 ◽  
Author(s):  
Ana R. Correia ◽  
Tao Wang ◽  
Elizabeth A. Craig ◽  
Cláudio M. Gomes
Keyword(s):  
Binding Capacity ◽  
Mitochondrial Protein ◽  
Thermal Stabilization ◽  
Autosomal Recessive Disorder ◽  
Binding Activity ◽  
Iron Binding ◽  
Functional Regions ◽  
Conformational Plasticity ◽  
Iron Binding Capacity ◽  
Β Sheet

Frataxin is a highly conserved mitochondrial protein whose deficiency in humans results in Friedreich's ataxia (FRDA), an autosomal recessive disorder characterized by progressive ataxia and cardiomyopathy. Although its cellular function is still not fully clear, the fact that frataxin plays a crucial role in Fe–S assembly on the scaffold protein Isu is well accepted. In the present paper, we report the characterization of eight frataxin variants having alterations on two putative functional regions: the α1/β1 acidic ridge and the conserved β-sheet surface. We report that frataxin iron-binding capacity is quite robust: even when five of the most conserved residues from the putative iron-binding region are altered, at least two iron atoms per monomer can be bound, although with decreased affinity. Furthermore, we conclude that the acidic ridge is designed to favour function over stability. The negative charges have a functional role, but at the same time significantly impair frataxin's stability. Removing five of those charges results in a thermal stabilization of ~24 °C and reduces the inherent conformational plasticity. Alterations on the conserved β-sheet residues have only a modest impact on the protein stability, highlighting the functional importance of residues 122–124.

Serum iron and total iron-binding capacity compared with serum ferritin in assessment of iron deficiency.

1981 ◽  
Vol 27 (2) ◽  
pp. 276-279 ◽  
Author(s):  
F Peter ◽  
S Wang
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Serum Iron ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Total Iron ◽  
Iron Binding ◽  
Total Iron Binding Capacity ◽  
Iron Deficient ◽  
Iron Binding Capacity

Abstract Ferritin values for 250 selected sera were compared with values for iron, total iron-binding capacity (TIBC), and transferrin saturation, to assess the potential of the ferritin assay for the detection of latent iron deficiency. The specimens were grouped (50 in each group) according to their values for iron and TIBC. In Group 1 (low iron, high TIBC) the saturation and ferritin values both indicated iron deficiency in all but one. In the 100 specimens of Groups 2 (normal iron, high TIBC) and 4 (normal iron, high normal TIBC), the saturation values revealed 16 iron-deficient cases, the ferritin test 55. For Groups 3 (low iron, normal TIBC) and 5 (low iron, low TIBC), the ferritin test revealed fewer cases of iron deficiency than did the saturation values (37 cases vs 51 cases, in the 100 specimens). Evidently the ferritin test detects iron deficiency in many cases for whom the serum iron and TIBC tests are not positively indicative. The correlation of serum ferritin with iron, TIBC, and transferrin saturation in the five groups was good only in the case of specimens for which the TIBC was normal; if it was abnormal the correlation was very poor.

scholarly journals Nontransferrin-bound iron in plasma from hemochromatosis patients: effect of phlebotomy therapy

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1416-1419 ◽  
Author(s):  
OI Aruoma ◽  
A Bomford ◽  
RJ Polson ◽  
B Halliwell
Keyword(s):  
Iron Overload ◽  
Binding Capacity ◽  
Radical Reactions ◽  
Iron Binding ◽  
Total Plasma ◽  
Free Radical Reactions ◽  
Low Concentrations ◽  
Idiopathic Hemochromatosis ◽  
Highly Correlated ◽  
Iron Binding Capacity

Abstract Plasma from patients with iron overload resulting from idiopathic hemochromatosis contains nontransferrin-bound iron, measurable by the bleomycin, assay. During venesection therapy, the concentration of bleomycin iron declines in a way highly correlated with plasma ferritin concentrations. Even when patients had been venesected to give very low total plasma iron concentrations and high transferrin iron-binding capacity, bleomycin-detectable iron was still present at low concentrations. Bleomycin-detectable iron can stimulate damaging free radical reactions, and its persistence in plasma even after prolonged venesection might contribute to the tissue damage that results from iron overload.

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