Low Serum Iron Levels Research Articles

The Potential Clinical Significance of the Serum Iron and Ferritin Status in Lung Cancer Patients

Background An increasing number of studies have shown that iron, one of the indispensable trace elements in the human body, is closely related to the occurrence and development of cancer. However, few studies have clearly demonstrated the role of the iron levels in lung cancer patients, or the potential effects of inflammation on iron levels. Methods The clinical data for lung cancer patients and non-lung cancer participants were retrospectively analyzed. The serum iron and ferritin levels were measured and compared using a rank-sum test. The correlation between the serum iron/ferritin and C-reactive protein (CRP) was analyzed by rank correlation. The cut-off values for continuous variables were obtained by the receiver operating characteristic curve (ROC) method. An analysis of potential prognostic factors in lung cancer patients was conducted by univariate and multivariate survival analyses. Results The serum iron levels in patients with extensive small-cell lung cancer (SCLC) were lower than those with limited-stage SCLC, and the levels of serum ferritin and CRP in those with extensive SCLC were higher than those with limited-stage SCLC. Similarly, the serum iron levels in patients with stage IV non-small cell lung cancer (NSCLC) were lower than those of patients with stage Ⅰ-Ⅲ disease, and the levels of serum ferritin and CRP in those with stage IV NSCLC were higher than those in stages Ⅰ-Ⅲ. The serum iron level was negatively correlated with the level of CRP, while the serum ferritin level was positively correlated with CRP. The stage of lung cancer, but not the serum iron/ ferritin level, was an independent prognostic factor in lung cancer patients. Conclusions The serum iron and ferritin levels are associated with the staging of lung cancer. The later stages of lung cancer are associated with a lower serum iron level, a higher serum ferritin level, and a higher CRP level. Inflammation may play an important role in regulating the serum iron and ferritin levels in lung cancer patients.

Iron, TIBC and Ferritin Levels Correlation with Testosterone Deficient Males in Dhaka, Bangladesh

Low serum iron and ferritin levels with an elevated TIBC are diagnostic of iron deficiency. While a low serum ferritin is virtually diagnostic of iron deficiency, a normal serum ferritin can be seen in patients who are deficient in iron and have coexistent diseases (eg, hepatitis or anemia of chronic disorders). Men with low testosterone levels have lower hemoglobin and hematocrit levels, while men with anemia of unknown etiology. Testosterone directly regulates body iron levels through inhibition of the master regulator of iron metabolism, hepcidin. In our study we studied with 30 males. 80.0% males were observed with low iron level, 100.0% found with normal ferritin level, 66.7% with normal TIBC and finally we found 96.7% males with low serum testosterone level. Keywords: Iron, TIBC, ferritin and testosterone. DOI: 10.7176/JHMN/81-10 Publication date: October 31 st 2020

Serum Iron and Ferritin Levels Are Correlated with Complement C3.

Iron is one of the most important trace elements in the body, and its homeostasis is essential to the normal function of the immune system. Complement component C3, which is the converging of three main pathways of complement system activation, plays a key role in the innate immunity. However, the relationship between iron homeostasis and complement C3 remains unknown. The aim of our study was to analyze the relationship between serum iron and ferritin level and complement C3 and C4. A total of 590 healthy individuals were recruited in our study. Higher serum complement C3 level (p < 0.001) was found in individuals with higher serum ferritin level (> 104.0μg/L). Moreover, serum iron level and serum ferritin level were positively correlated with complement C3 (r = 0.133, p = 0.001; r = 0.221, p < 0.001) and complement C4 (r = 0.117, p = 0.004; r = 0.123, p = 0.003). The linear regression analysis displayed that both serum iron level and serum ferritin level were linearly correlated with serum complement C3 level (adjusted beta: 2.382, 95% CI: 0.841-3.923; adjusted beta: 42.911, 95% CI: 29.070-56.751). To explore the relationship between iron homeostasis and complement C3 further, the serum samples from C3-/- mice and the wild-type (WT) control mice were obtained. Significantly lower serum iron level and higher ferritin level were found in C3-/- mice than those in WT mice (p < 0.001; p < 0.001), indicating that complement C3 might influence iron distribution and utilization. Overall, these data suggested that serum iron and ferritin levels were correlated with complement C3. The deficiency of complement C3 may disrupt the regular iron metabolism in the body.

Study the iron status in children with febrile seizures: a hospital based cross sectional study

Background: Febrile seizures are most common among childhood seizures, accounts to 2% to 5% in children below 5 years of age. Iron deficiency can cause many neurological deficits and may lower the seizure threshold. The present study was conducted to determine the iron status in children with febrile seizures.Methods: The present cross-sectional study was conducted in the Department of Pediatrics, HIMS, Dehradun, over a period of 12 month from January 2018 to December 2018. A total of 105 children of age group 6 month to 5 years, coming to pediatrics department were included in the study. Total study subjects were divided into two groups, Group I (febrile seizure) and Group II (other than febrile seizure). A consecutive sampling method was done for selection of study subjects.Results: In Group I (febrile seizure), the number of males were 71.7% while females were 28.3% with male: female ratio of 2.5:1. In Group I (febrile seizure), 61.7% of subjects had deficient iron level while 38.3% of subjects had normal serum iron level. Our study shows significantly low mean serum ferritin and mean serum iron level in subjects with febrile seizures.Conclusions: We concluded that iron deficiency is more common in febrile seizures and there is a positive association between serum iron level and febrile seizures.

Serum Iron Level as a Potential Predictor of Coronavirus Disease 2019 Severity and Mortality: A Retrospective Study.

BackgroundVarious types of pulmonary diseases are associated with iron deficiency. However, information on iron status in coronavirus disease 2019 (COVID-19) is scarce.MethodsThis study included 50 hospitalized patients with confirmed COVID-19. The role of serum iron in predicting severity and mortality of COVID-19 was evaluated.ResultsThe most common symptoms of COVID-19 patients in this study were cough (82%), fever (64%), and chest distress (42%). Of the 50 patients, 45 (90%) patients had abnormally low serum iron levels (<7.8 μmol/L). The severity of COVID-19 was negatively correlated with serum iron levels before and after treatment and was positively correlated with C-reactive protein, serum amyloid A, D-dimer, lactate dehydrogenase, urea nitrogen, and myoglobin levels. Decreased serum iron level could predict the transition of COVID-19 from mild to severe and critical illness. Seven (53.8%) patients with a lower serum iron level after treatment in the critical group had died. There was a significant difference in posttreatment serum iron levels between COVID-19 survivors and nonsurvivors.ConclusionsSerum iron deficiency was detected in the patients with COVID-19. The severity and mortality of the disease was closely correlated with serum iron levels. Low serum iron concentration was an independent risk factor for death in COVID-19 patients.

Low serum iron levels and risk of cardiovascular disease in high risk elderly population: Nested case-control study in the PREvención con DIeta MEDiterránea (PREDIMED) trial.

Epidemiological data on iron status and cardiovascular disease (CVD) are still controversial. The aim of this study was to determine whether low serum iron (SI) levels are associated with an increased odds of first CVD event in a population at high cardiovascular risk. Case-control study design nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke or cardiovascular death) during follow-up period (2003-2010) were matched by sex, age and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. Inductively coupled plasma mass spectrometry analysis was used to determine SI levels. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. Multivariable-adjusted odds ratios (ORs) of CVD were calculated with conditional logistic regression. Mean SI levels were higher in men than in women (1224.0μg/L vs. 1093.8μg/L; p<0.001). Among women, but not in men, the mean SI concentration was lower in cases than in controls (1008.5μg/L vs. 1132.9μg/L; p=0.030). There was a gradual decrease in the multivariable-adjusted ORs of CVD with increasing SI levels (highest vs. lowest quartile: OR=0.55, 95% CI: 0.32-0.93; ptrend=0.020). This inverse relationship was more pronounced among women (highest vs. lowest quartile: OR=0.15, 95% CI: 0.03-0.69; ptrend=0.011). The present findings are consistent with previously reported inverse associations between SI and CVD. SI levels as an independent marker of short-term cardiovascular risk may be useful for risk assessment in older populations. www.controlled-trials.com; International Standard Randomized Controlled Trial Number (ISRCTN): 35,739,639. Registered 5 October 2005. Retrospectively registered.

Iron status is linked to disease severity after avian influenza virus H7N9 infection.

The high mortality rate of H7N9 strain of avian influenza virus (AIV) infected patients has been a major clinical concern. Iron overload increases the susceptibility of host for several kinds of microbial infection. However, the study on patients' iron and ferritin status associated with clinical outcome of AIVH7N9 virus infection is poorly understood, and in order to explain the linkage we carried out this study. We retrospectively collected serum from 46 patients infected with H7N9 virus from the hospital in Hangzhou city, Zhejiang province of China in 2013. We measured the level of serum iron and ferritin by Enzyme-Linked Immunosorbent Assay (ELISA). The correlation analysis of iron and ferritin with disease severity was done by SPSS 16.0 and MedCalc Software. After H7N9 infection, there is a reduction in iron level and an increase in ferritin, hepcidin and C-reactive protein (CRP) level in patient's serum compared to those of the control (p<0.001), and there's little correlation between procalcitonin (PCT) level and H7N9 infection. At week 1 and week 2 post-infection, serum iron level is much lower and ferritin level is much higher in the patients who died later than those in the patients who survived. The sensitivity, specificity, and Area Under the Curve (AUC) of the assay was calculated with MedCalc software and they were 85.5%, 65.9% and 0.803 for iron and 84.9%, 80.7% and 0.900 for ferritin, 95.2%, 51.1% and 0.684 for PCT and 100%, 94.6% and 0.988 for CRP, respectively. Our study found that low serum iron and high serum ferritin levels are correlated with the disease severity of H7N9-infected patients and can predict fatal outcomes.

Attention-Deficit/Hyperactivity Disorder Patients May Have Undiagnosed Narcolepsy.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) patients have many comorbidities. Narcoleptic patients have a big prevalence of ADHD (15%-30%). Both groups suffer from similar symptoms and benefit from the same class of medications. As such, narcolepsy could be masked in ADHD patients. Low serum ferritin has been found both in ADHD patients as well as in patients with narcolepsy.Materials & methodsWe enrolled 26 participants (14 ADHD patients and 12 controls). They answered several questionnaires, and blood samples were obtained from 20 participants. We had clear exclusion criteria.ResultsUsing the Ullanlinna Narcolepsy Scale (UNS), we identified three possible narcolepsy patients within the ADHD group and no suspects in the control group. There was a statistically significant negative correlation between serum iron levels and ADHD symptom severity. No correlation was found measuring serum ferritin levels.ConclusionsNarcolepsy may be more common within ADHD patients than in the general population. Some of these patients could benefit from a change in medication. Low serum iron and ferritin levels could be relevant in ADHD pathophysiology. This requires further exploratory research.

A Spore‐Forming Probiotic Supplement Improves the Intestinal Immune Response and Protects the Intestinal Health During Recurrent Clostridioides difficile Colonization in Mice

Around 15%-30% of patients develop recurrent Clostridioides difficile infection (CDI) as conventional therapies disrupt protective gut microbiota. We tested if supplementation with a spore-forming probiotic would protect intestinal health in a mouse model of recurrent CD colonization. Methods: Female CF-1 mice were exposed to CD spores (4-log10 colony-forming units/10 μL) and then randomly assigned to receive either saline (CD-S) or probiotic (CD-PRO). Control mice received only saline (control). Following confirmation of initial CD colonization, mice were treated with vancomycin (10 days). After 5 days, mice recolonized with CD were treated again with vancomycin (10 days) and euthanized 5 days later. Fecal samples were collected at select time points for bacterial analysis. Following euthanasia, blood samples, cecum contents, and the intestine were collected for analysis. Probiotic supplementation mitigated the antibiotic-induced changes in cecum weight (P < .001). Probiotic-supplemented mice had increased messenger RNA expression of several immune parameters, accompanied by lower serum iron levels compared with CD-S mice (P < .05). Lower expressions of TNF α and calprotectin (P ≤ .05) were observed in CD-PRO mice compared with CD-S. The probiotics also supported the expression of intestinal tight junction proteins, which were diminished in the proximal colon of CD-S mice (P < .05). Mice supplemented with targeted spore-forming probiotics exhibited improved immune responses and nutrition immunity properties, which were linked with less inflammation and enhanced intestinal barrier proteins during recurrent CD colonization.

Association of Serum Iron and Ferritin Levels in Patients of Cholelithiasis: A Cross-Sectional Study

Background: Cholelithiasis is a common abdominal disorder resulting in increasing hospital admissions. About 10-12% of adults develop gallstones. Aim of this study was to find out any association of serum iron and ferritin levels in patients of cholelithiasis. Subjects and Methods: Present study was conducted at the department of surgery, tertiary care institute of for the period 1 year. For the study purpose 70 gall stone cases and 70 normal healthy matched controls were taken as study participants. After explaining about the study to the subjects, an informed consent will be obtained, followed by a detailed history with clinical examination with more emphasis on the parameters given below in outcome variable (ultrasonography finding, serum iron level, serum ferritin level, serum cholesterol). Results: The mean age in the case group (gallstones present) is 43.12 years, as compared to the control group the mean age is 41.05 years, The study shows in the case group 64% of patient was female and 36% was male and in the control group 76% of patient was female and 24% was male. In this study 46 (65.7%) patients with gallstones have the value of serum iron less than normal (normal value: &gt;40 µg/dl). Our study shows, there are 35 female patients with gallstone disease who have serum iron levels below the normal value Most of the patients with gallstone disease whose serum iron levels are subnormal are females. Our study shows that the mean serum iron between cases and control was statistically significant p 0.05. There is no effect of anemia on serum cholesterol. In this study the mean serum cholesterol between cases and control was statistical insignificant (p&gt;0.7)) In the case group, 20 of male and 36 of female patients have normal serum ferritin levels. The number of females having normal serum ferritin levels (in both case and control groups) is more. Conclusion: Gallstones are more prevalent in female population than males. Serum ferritin association is insignificant as it increases other condition with inflammation also. Low serum iron level associated with high risk of cholelithiasis as this may lead to super saturation of bile.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease complicated with chronic heart failure: a retrospective cohort study.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease (CHD) complicated with chronic heart failure (CHF) is still unclear. The objective of this study was to explore the effects of serum iron level without anemia on long-term prognosis of patients with CHD complicated with CHF. In this retrospective cohort study, 221 patients with CHD complicated with CHF were consecutively investigated. These patients were divided into three groups according to the tertiles of the serum iron level: low-iron group (n = 71), medium-iron group (n = 76) and high-iron group (n = 74). The overall serum iron without anemia was 13.0 ± 5.50 μmol/L and serum iron in each group was 7.58 ± 1.63 μmol/L, 11.94 ± 1.79 μmol/L, and 19.37 ± 3.81 μmol/L, respectively. Composite endpoint events were composed of major adverse cardiovascular and cerebrovascular events (MACCE), including recurrent heart failure, all-cause death, acute coronary syndrome (ACS) and ischemic stroke. The median follow-up duration was 239days. After adjusting relevant confounding risk factors, we found that excessively low or high serum iron level is correlated to the MACCE in patients with CHD complicated with CHF and that the prognosis of patients with excessively high serum iron level is poorer than that of patients with excessively low serum iron level. We further revealed the effect of serum iron level on MACCE is U-shaped, but not linear relationship. Sensitivity analysis showed that the correlation between serum iron level and MACCE is stable. In addition, according to the test for interaction, the variables that modify the effect including CRP (P for interaction < 0.0001), diuretics (P for interaction = 0.0212) and antiplatelet drugs (P for interaction = 0.0167). This study showed that excessively low or high serum iron level without anemia is an independent risk factor of MACCE in patients with CHD complicating with CHF.

Serum iron levels are negatively correlated with serum triglycerides levels in female university students.

Dyslipidemia is common among the general population, and its prevention is urgently needed particularly for the health of students. The purpose of our study was to explore the relationship between serum iron level and blood lipids. A sample of 290 university students was collected in this cross-section study. The blood lipids and serum iron levels were determined. Pearson's correlation coefficient was used to determine the correlation between serum iron level and blood lipids. The prevalence of dyslipidemia was 8.8% among male students and 5.4% among female students. The overall prevalence of dyslipidemia was7.2% among the total students. The results showed that serum iron level was negatively correlated with triglyceride (TG), but was positively correlated with high-density lipoprotein cholesterol (HDL)-cholesterol, low-density lipoprotein cholesterol (LDL)-cholesterol, and total cholesterol (TC) in female students. Female students with serum iron less than 15 mmol/L had higher levels of serum TG than female students with serum iron 15 mmol/L or above (P<0.05). These findings suggest that lower serum iron levels may be a risk factor of high serum TG in female students. Supplementation of iron may be a strategy for prevention of high serum TG in female students.

Could iron-chelation with EDTA and bloodletting/transfusion be a therapeutic option in COVID-19 worst scenario? Proposal for a protocol

COVID-19 is a complex, multi-organ disease where lungs are primarily affected, resulting in a form of ARDS in the later stages. In fact, a relevant role has been attributed to iron dysmetabolism and series of literature data highlight a clear-cut alteration in a few related parameters; significantly high figures of ferritin, hepcidin, red blood cell width distribution, lactate dehydrogenase and lactate, in combination with low levels of serum iron and transferrin, have been repeatedly reported in patients affected by Sars-Cov-2 infection at later stages. Overall, these alterations have a negative prognostic value, indicating a pattern of ferroptosis and of a possible dysfunctional hemoglobin, with pro-coagulant and pro-inflammatory repercussions. Different pathomechanisms have been proposed, from erythrocyte attack and an hepcidin-mimetic action of the viral spike proteins, to a more general iron and calcium deregulated intracellular accumulation. Iron chelation has been advocated as one of the possible treatments of COVID-19 and CaNa2ethylendiaminetetraacetic acid (EDTA) is known as a safe and effective mineral-chelator. In this review the authors propose an EDTA-based therapeutic protocol for those patients in most critical stages and admitted to intensive care unit, with the aim to reduce intracellular and blood ferritin overload. Bloodletting and blood transfusion have proved to be beneficial in patients with viral disease-associated iron accumulation. The inclusion of these two procedures in the proposed protocol aims at improving oxygenation by new normo-functioning hemoglobin, while decreasing toxic hyperferritinemia and interleukins. Lastly, a few specific compounds are also taken into consideration to synergistically complement EDTA infusion. A series of technical details are provided for the possible use of the protocol in clinical practice.

Correlation Analysis Between Preoperative Serum Iron Level and Prognosis as Well as Recurrence of HCC After Radical Resection.

BackgroundThe purpose of this retrospective study was to investigate the relationship between serum iron levels and the prognosis and risk of recurrence in patients with hepatocellular carcinoma (HCC).MethodsA total of 253 HCC patients who underwent radical resection were involved in this study.ResultsAccording to the receiver operating characteristic (ROC) curve, the optimal cut-off value for preoperative serum iron in the assessment of HCC postoperative prognosis was 94 ug/dL. The overall survival (OS) of patients in the high iron group was significantly better than that in the low iron group (p < 0.001). The recurrence rate of patients in the low iron group was higher than that in the high iron group (p = 0.011). Correlation analysis showed that preoperative serum iron level was correlated with tumor size >5 cm (χ2 = 11.590, p < 0.001), recurrence (χ2 = 5.714, p = 0.017) and microvascular invasion (χ2 = 5.087, p = 0.024). In addition, univariate analysis showed that OS and disease-free survival (DFS) of HCC patients with high iron level were better than those with low iron level. Furthermore, multivariate COX proportional hazards regression analysis showed that serum iron ≤94 μg/dL, tumor size >5 cm, and microvascular invasion were independent predictors for shorter OS and DFS in HCC patients after operation, while recurrence was for shorter OS.ConclusionPatients with low preoperative serum iron level had worse postoperative survival and higher recurrence rate in HCC. Preoperative serum iron is an independent predictor of HCC patients. For HCC patients with low iron levels, prognosis of patients may be improved if appropriate iron is supplemented.

Recurrent aphthous stomatitis as the only clinical sign of celiac disease in obese adolescent - case report and literature review

Introduction. Recurrent aphthous stomatitis (RAS) is a relatively common oral mucosal lesion of unclear etiology. It occurs in otherwise healthy people, but also in various infectious and non-infectious diseases, including celiac disease (CD). We present an obese adolescent with RAS as the only clinical sign of CD. Case outline. An adolescent aged 15 2/12 years come with very pronounced RAS in previous five months. He had no other difficulties. The patient was obese from the age of 12. Other data were without peculiarities. On admission he was 165 cm tall (P25), obese (BMI 27 kg/m2), in the final stage of puberty, with stretch marks in the distal areas of the abdomen, thighs and gluteus and very pronounced pain-sensitive aphthae in the buccal and labial mucosa accompanied by swelling of the lips and perioral region. Except for lower serum iron levels (8 ?mol/l), routine laboratory blood tests were within the reference range. The serological test for CD was positive (antibodies to tissue transglutaminase IgA 78.5 U/ml, anti-endomysial antibodies IgA positive). Endoscopy revealed reflux esophagitis, without any other pathological findings. Stereomicroscopic and pathohistological analysis of the duodenal mucosa samples showed mild destructive enteropathy (Marsh IIIa). Pathohistological examination of the gastric mucosa revealed grade I-II lymphocytic gastritis. The urease test for Helicobacter pylori was negative. A gluten-free diet resulted in the withdrawal of aphthous stomatitis and no recurrence later. Conclusion. Within the differential diagnostic analysis of the RAS causes, CD should also be considered. Additionally, obesity does not exclude the presence of CD.

The prevalence of anemia among children infected with Entamoeba histolytica in Baghdad

The relation between Entamoeba histolytica and anemia has lately had much attention. The aim of this study was to determine the possible correlation between anemia and parasitic intestinal infection with E.histolytica in children from Baghdad-Iraq. This study was conducted from October 2018 to April 2019 in different hospitals, primary health care centers, and primary schools. Eighty-one children participated in this study and their ages were between 1 and 12 years. The participants were divided into two groups based on their general microscopic stool examination. The first group was diagnosed as E.histolytica infected group (n=47), while no pathogens were detected in the stool samples of the second group which was considered as a healthy control (n=34). Blood samples were taken from all subjects and tested for haemoglobin level, serum ferritin, serum iron, total binding iron capacity (TBIC) and mean corpuscular volume (MCV). Nutritional status was also evaluated for all children aged ≥5 years old. Results showed that the prevalence of anemia was higher in children infected with E.histolytica compared with the control subjects. Anemia was largely reported among children aged 1-3 years for both E.histolytica infected children and control subjects. The results also illustrated that both haemoglobin and iron levels were significantly (p˂0.05) lower in E.histolytica infected children compared with control subjects, while non-significant differences (p˃0.05) were observed in the level of ferritin between E.histolytica infected children and control subjects, although the ferritin was lower in E.hisolytica infected group. The results showed that both gender and age are significantly related to low serum iron levels in both infected and control groups. Significant relationshipswere also noticed between each of the anemia types and the nutritional status with the E.histolytca infection. Microcytic anemia as well as high records of severe malnutrition were observed in the majority of E. histolytica infected children&#x0D; These findings indicate that anemia is more expected to be present in children infected with E.histolytica. Therefore, efforts should be focused on health education of populations at high risk of both anemia and E.histolytica.

Ferroportin in Erythrocytes: Importance for Iron Homeostasis and its Role in Infection

Ferroportin (FPN), the only known vertebrate iron exporter, transports iron from intestinal, splenic, and hepatic cells into the blood to provide iron to other tissues and cells in vivo. Most of the circulating iron is consumed by erythroid cells to synthesize hemoglobin. Recently, we found that erythroid cells not only consume large amounts of iron, but also return significant amounts of iron to the blood. Erythroblast-specific Fpn knockout (Fpn KO) mice developed lower serum iron levels in conjunction with tissue iron overload and increased FPN expression in spleen and liver without changing hepcidin levels. Our results also showed that Fpn KO mice, which suffer from mild hemolytic anemia, were sensitive to phenylhydrazine-induced oxidative stress but were able to tolerate iron deficiency upon exposure to a low-iron diet and phlebotomy, supporting that the anemia of Fpn KO mice resulted from erythrocytic iron overload and resulting oxidative injury rather than a red blood cell (RBC) production defect. Moreover, we found that the mean corpuscular volume (MCV) values of gain-of-function FPN mutation patients were positively associated with serum transferrin saturations, whereas MCVs of loss-of-function FPN mutation patients were not, supporting that erythroblasts donate iron to blood through FPN in response to serum iron levels. Our results indicate that FPN of erythroid cells has an unexpectedly essential role in maintaining systemic iron homeostasis and protecting RBCs from oxidative stress, providing insight into the pathophysiology of FPN diseases. When malaria parasites invade red blood cells (RBCs), they consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. We recently found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation,Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPNQ248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection. Zhang DL, Wu J, Shah BN et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018;359 (6383):1520-1523. Zhang DL, Ghosh MC, Ollivierre H, Li Y, Rouault TA. Ferroportin deficiency in erythroid cells causes serum iron deficiency and promotes hemolysis due to oxidative stress. Blood. 2018;132 (19):2078-2087. Zhang DL, Rouault TA. How does hepcidin hinder ferroportin activity. Blood. 2018;131 (8):840-842. Disclosures No relevant conflicts of interest to declare.

The iron and testosterone levels in amoebic liver abscess patients - a preliminary study from northern Sri Lanka

Amoebic liver abscesses (ALA) are observed among adult males who consume locally brewed alcohol in the tropics. The contributory role of alcohol-induced hepatic iron stores and the male hormone testosterone were said to be playing a pivotal role in the pathogenesis of ALA. This descriptive preliminary study was intended to see a possible relationship of serum iron profile and testosterone level among toddy (a local palm wine) drinkers who presented with ALA to the Teaching Hospital Jaffna. Results have shown very high serum ferritin levels (902.58ng/ml) in these patients with ALA. However, the serum iron levels (43.05µg/dl) and the transferrin saturation levels (22.01%) were observed to be normal or below normal and Total Iron Binding Capacity (TIBC) level was unexpectedly low (193.3µg/dl) for the corresponding low serum iron levels. Furthermore, the serum testosterone level (2.44ng/ml) was also low or low normal when compared with the reference range in the study population. As this preliminary study contrasts with previously postulated theories, further study is recommended to arrive at a concrete conclusion.

Ferroportin-mediated iron export from vascular endothelial cells in retina and brain

Retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD) and other neurodegenerative diseases. The retina and the brain are protected from the systemic circulation by the blood retinal barrier (BRB) and blood brain barrier (BBB), respectively. Iron levels within the retina and brain need to be tightly regulated to prevent oxidative injury. The method of iron entry through the retina and brain vascular endothelial cells (r&bVECs), an essential component of the BRB and BBB, is not fully understood. However, localization of the cellular iron exporter, ferroportin (Fpn), to the abluminal membrane of these cells, leads to the hypothesis that Fpn may play an important role in the import of iron across the BRB and BBB. To test this hypothesis, a mouse model with deletion of Fpn within the VECs in both the retina and the brain was developed through tail vein injection of AAV9-Ple261(CLDN5)-icre to both experimental Fpnf/f, and control Fpn+/+ mice at P21. Mice were aged to 9 mo and changes in retinal and brain iron distribution were observed. In vivo fundus imaging and quantitative serum iron detection were used for model validation. Eyes and brains were collected for immunofluorescence. Deletion of Fpn from the retinal and brain VECs leads to ferritin-L accumulation, an indicator of elevated iron levels, in the retinal and brain VECs. This occurred despite lower serum iron levels in the experimental mice. This result suggests that Fpn normally transfers iron from retinal and brain VECs into the retina and brain. These results help to better define the method of retina and brain iron import and will increase understanding of neurodegenerative diseases involving iron accumulation.

A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism

BackgroundManganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity.Case presentationA 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up.ConclusionThe syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.