Higher Serum Transferrin Saturation Research Articles

Ferritin Increase in Hemochromatosis Subjects After Discontinuing Their Regular Maintenance Treatment: A Longitudinal Analysis Performed During the COVID-19 Imposed Hospital Lockdown.

Ferritin Increase in Hemochromatosis Subjects After Discontinuing Their Regular Maintenance Treatment: A Longitudinal Analysis Performed During the COVID-19 Imposed Hospital Lockdown.

Association of serum chromium levels with malnutrition in hemodialysis patients

BackgroundChromium is an essential trace metal that reduces oxidative stress and inflammation. In patients undergoing maintenance hemodialysis (MHD), a correlation among chromium exposure, inflammation, and malnutrition remains unclear. This study examined the possible effects of serum chromium levels (SCLs) in MHD patients.MethodsInitially, 732 MHD patients in dialysis centers were recruited. A total of 647 patients met the inclusion criteria and were stratified by SCL into four equal-sized groups: first quartile (< 0.29 μg/L), second quartile (0.29–0.56 μg/L), third quartile (0.57–1.06 μg/L), and fourth quartile (> 1.06 μg/L). Demographic, biochemical, and dialysis-related data were obtained for analyses. The analysis included nutritional and inflammatory markers.ResultsAs compared with the highest quartile group, more subjects in the lowest quartile group were of an older age; had lower hemoglobin and creatinine levels; had a higher prevalence of DM and malnutrition (serum albumin level < 3.6 g/dL); and higher serum transferrin saturation and ferritin levels. A stepwise multiple linear regression analysis revealed a significant negative correlation between malnutrition and SCL (β coefficient = − 0.129, p = 0.012) and negative associations among body mass index (β coefficient = − 0.010, p = 0.041), ferritin (β coefficient = − 0.107, p = 0.001) and SCL. A multivariate logistic regression analysis also demonstrated a negative correlation between malnutrition and SCL. With a 10-fold increase in SCL, the risk ratio of malnutrition was 0.49 (95% confidence interval: 0.25–0.96; p = 0.039).ConclusionsSCL is significantly associated with malnutrition in MHD patients. Further evaluation of the relationship between clinical outcomes (morbidity/mortality) and SCL is necessitated.

Variable expressivity of HJV related hemochromatosis: “Juvenile” hemochromatosis?

Juvenile hemochromatosis is a rare autosomal recessive disease due to variants in the Hemojuvelin (HJV) gene. Although biological features mimic HFE hemochromatosis, clinical presentation is worst with massive iron overload diagnosed during childhood.Our study describes clinical features and results of genetic testing for a group of patients initially referred for a hepcidino-deficiency syndrome and for whom HJV hemochromatosis was finally diagnosed. 662 patients with iron overload and high serum transferrin saturation were tested, and five genes (HFE, HJV, HAMP, TFR2, SLC40A1) were sequenced.Among our cohort, ten unrelated patients were diagnosed with HJV hemochromatosis. Genetic testing revealed five previously published and five undescribed variants: p.Arg41Pro, p.His180Arg, p.Lys299Glu, p.Cys361Arg and p.Ala384Val.Surprisingly, this study revealed a late age of onset in some patients, contrasting with the commonly accepted definition of “juvenile” hemochromatosis. Five of our patients were 30 years old or older, including two very late discoveries. Biological features and severity of iron overload were similar in younger and older patients.Our study brings new insight on HJV hemochromatosis showing that mild phenotype and late onset are possible. Genetic testing for HJV variants should thus be performed for all patients displaying a non-p.Cys282Tyr homozygous HFE hemochromatosis with hepcidin deficiency phenotype.

Cancer risk in HFE C282Y homozygotes: results from the HUNT 2 study

Objective. In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes. Material and methods. We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995–1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking. Results. Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60–2.03] in women and 0.94 [95% CI 0.53–1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17–7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68–1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35–3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence. Conclusions. C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk.

Transferrin Saturation and Hospital Length of Stay and Mortality in Medicare Beneficiaries

To evaluate in a large, nationally representative cohort the association between high serum transferrin saturation (TS) and hospital length of stay and mortality in older adults. Prospective cohort. Longitudinal analyses of the Third National Health and Nutrition Examination Survey linked to Medicare claims from 1991 through 2006. Medicare beneficiaries aged 65 and older at baseline. Transferrin saturation collected on each participant at baseline was characterized as <20.0%, 20.0% to 54.9%, and 55.0% and greater. Length of stay in the hospital and death in the hospital were primary outcomes. Analyses were adjusted for age, sex, race and ethnicity, education, and severity of illness. Individuals hospitalized during the study period (79.4%) with high (odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.05-6.12) or low (OR = 1.31, 95% CI = 1.07-1.62) TS had a significantly greater risk of death than those with moderate TS. Individuals with high TS had longer average length of stay per hospitalization (11.1 days, (standard error, SE 1.7 days), P = .01) than those with moderate TS (8.4 (0.3) days). Individuals with high TS also had more hospital days per year (8.6 (2.0) days, P = .04) than those with moderate TS (6.7 (0.5) days). High TS is associated with longer length of stay and death in the hospital (unweighted N = 3,847, weighted N = 28,395,464).

Hereditary hemochromatosis: the clinical significance of the S65C mutation.

Hereditary hemochromatosis (HH) is a common genetic disease with iron overload in certain organs, especially the liver. Most cases are homozygous for the C282Y mutation in the HFE gene; a few are C282Y heterozygous, compound C282Y/H63D heterozygous, or have no known mutation. A third mutation, S65C, has been associated with HH, but this finding is disputed. We have studied the clinical significance of various genotypes with the S65C mutation. In a population-based screening for HH in 65,238 persons, 613 had high serum transferrin saturation in two blood samples and were invited for HFE genotyping. In 556 persons with complete data sets, we studied the serum ferritin concentration and the risk of being diagnosed with phenotypic HH in the various genotypic groups. The phenotypic diagnosis was given without knowing the genotypic result. Except for the C282Y homozygotes, no differences in median serum ferritin concentrations were found between the various genotypic groups. However, the C282Y/S65C compound heterozygous group had a higher risk of being diagnosed with phenotypic HH than the wild-type group, as did the C282Y homozygous and the C282Y/H63D compound heterozygous groups. When combined with the C282Y mutation, the S65C mutation is associated with an increased risk of being diagnosed with phenotypic HH.

Screening for Hemochromatosis: High Prevalence and Low Morbidity in an Unselected Population of 65,238 Persons

Background: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in several organs, most notably the liver. The C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent clinical disease and to study the cost and feasibility of screening, a large population was screened. Methods: In a Norwegian county, all inhabitants 20 years or older were invited to participate in a population-based health survey programme. Screening for HH was one of several subprojects. Blood samples were obtained from 65,238 persons. Subjects with high serum transferrin saturation in two tests and high serum ferritin were clinically evaluated for HH. All subjects with high serum transferrin saturation in two tests were offered genotyping. Results: HH was newly diagnosed in 92 women and 177 men. Phlebotomy treatment was performed in 64 women and 152 men. Severe organ damage (liver cirrhosis) was ascertained in only 4 men. We found no correlation between serum ferritin and age. The estimated cost was US$ 1.6 per subject screened and US$ 390 per newly discovered HH subject. The estimated prevalence of phenotypical HH not previously known was 0.34% in women and 0.68% in men. The prevalence of the C282Y/C282Y mutation was at least 0.68%. Conclusion: Large-scale screening for HH can be performed at a relatively low cost if combined with a health survey programme. The yield in terms of newly discovered cases is considerable, but few cases were found seriously ill. Better knowledge of the natural course of HH is necessary if we are to be able to estimate the cost-effectiveness of large-scale screening.

Hereditary haemochromatosis as an immunological disease.

Hereditary haemochromatosis as an immunological disease.

Body Iron Stores May Modify Sensitivity to Occupational Radiation Exposure

Abstract Iron is the most abundant transition metal in humans, and it plays a central role in metabolism. However, excess physiological iron may be toxic; it may increase the risk of cancer; and it has now been shown to increase cellular sensitivity to radiation injury. Increased available iron stores may enhance cell killing and genetic alterations through catalysis of free-radical reactions. This may lead to direct DNA damage or depletion of cellular reserves of reducing equivalents, thereby interfering with the maintenance of genomic integrity. Human epidemiological studies are being conducted to determine the effect of excess iron on cancer risk; experimental laboratory studies are probing the increased risk of radiation injury. In prospective studies of a sample of the U.S. population, high serum transferrin saturation was found to correlate directly with cancer risk over a 10-year period. In experimental studies using Chinese hamster ovary cells, ferritin (∼19% iron by weight) added to the growth me...

Association of serum iron, serum transferrin saturation, and serum ferritin with survival in acute lymphocytic leukemia.

The present investigation was motivated from the consideration that a host environment rich in iron, represented by high serum transferrin saturation (TS) and high serum iron and serum ferritin levels might offer favorable growth conditions for leukemic cells in addition to infection, thus affecting survival. Serum measurements were obtained on 113 pediatric patients with acute lymphoblastic leukemia (ALL), seen at Memorial Sloan-Kettering Cancer Center between May 20, 1981 and August 8, 1983. A significant difference (p less than 0.001) was found between the survival of patients according to whether their first measured TS was greater than 36% or less than 36%, with fewer deaths in the group with TS less than 36. The relationship between TS and survival was still observed when patients were stratified according to length of time from diagnosis, risk group, French-American-British (FAB) classification, or presence of organomegaly at diagnosis (p less than 0.001). Similar differences were observed between survival of patients grouped according to their first measured serum ferritin. These results independently confirm and extend observations presented earlier and support the consideration that motivated this study. The value of serum iron-related measurements as prognostic variables cannot be established from this type of study; however, these findings suggest the need for a prospective study.