Iron overload syndrome

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in NUP98-HOXD13 transgenic mice, a highly penetrant well-established MDS mouse model...

Iron is an essential trace element for organisms. However, iron overload, which is common in haematological disorders (e.g. haemochromatosis, myelodysplastic syndromes, aplastic anaemia, and thalassaemia, blood transfusion-dependent or not), can promote reactive oxygen species generation and induce ferroptosis, a novel form of programmed cell death characterised by excess iron and lipid peroxidation, thus causing cell and tissue damage. Infertility is a global health concern. Recent evidence has indicated the emerging role of iron overload and ferroptosis in female infertility by inducing hypogonadism, causing ovary dysfunction, impairing preimplantation embryos, attenuating endometrial receptivity, and crosstalk between subfertility-related disorders, such as polycystic ovary syndrome and endometriosis...

BACKGROUND: There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. We aimed to validate the clinical outcomes of MHF in general population and biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) patients. METHODS: NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males] - 550 ng/ml; grade 2: 550 - 1000 ng/ml; grade 3: > 1000 ng/ml)...

BACKGROUND: Most patients with lower risk myelodysplastic neoplasms (MDS) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron overloaded RBC transfusion-dependent patients with lower risk MDS...

PURPOSE (BACKGROUND): The presented review is an updating of Iron metabolism in context of normal physiology and pathological phases. Iron is one of the vital elements in humans and associated into proteins as a component of heme (e.g. hemoglobin, myoglobin, cytochromes proteins, myeloperoxidase, nitric oxide synthetases), iron sulfur clusters (e.g. respiratory complexes I-III, coenzyme Q10, mitochondrial aconitase, DNA primase), or other functional groups (e.g. hypoxia inducible factor prolyl hydroxylases)...

Thalassemia, a congenital hemoglobinopathy, is characterized by impaired erythropoiesis and peripheral hemolysis, leading to anemia. Thalassemia major, in particular, necessitates regular blood transfusions, resulting in iron accumulation in the body. Iron overload primarily affects the heart and can induce cardiac disorder, including defects in the pump and conduction system, which is one of the leading causes of mortality among thalassemics. The existing literature has revealed limited support for the occurrence of acute coronary syndrome (ACS) due to hemochromatosis...

PURPOSE: To determine the rate and clinical characteristics associated with abnormal thyroid and adrenal function in recipients of nonmyeloablative hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) and beta-thalassemia. METHODS: We retrospectively reviewed patients who enrolled in 4 nonmyeloablative HCT regimens with alemtuzumab and total body irradiation (TBI). Baseline and annual post-HCT data were compared, which included age, sex, sickle phenotype, thyroid panel (total T3, free T4, thyroid stimulating hormone, antithyroid antibodies), cortisol level, ACTH stimulation testing, ferritin, medications, and other relevant medical history...

Obtaining an imaging diagnosis of various hepatobiliary and pancreatic disorders caused by certain drugs can often be challenging. Familiarity with these conditions may improve diagnostic accuracy and patient management. This review aimed to describe the imaging findings of drug-associated hepatobiliary and pancreatic disorders and identify suggestions for obtaining a correct diagnosis. We focused on relatively common disorders or those that can present with characteristic imaging findings, such as drug-induced acute hepatitis, sinusoidal obstruction syndrome, focal nodular hyperplasia-like lesions, hepatocellular adenoma, pseudocirrhosis, chemotherapy-associated steatohepatitis, amiodarone deposition in the liver, secondary iron overload, drug-induced pancreatitis, pancreatic enlargement after epoprostenol therapy, ceftriaxone-associated gallbladder pseudolithiasis, immune-related adverse events, and methotrexate-associated lymphoproliferative disorders...

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing the requirement for RBC transfusions...

It is well documented that diabetes mellitus (DM) is strongly associated with cognitive decline and structural damage to the brain. Cognitive deficits appear early in DM and continue to worsen as the disease progresses, possibly due to different underlying mechanisms. Normal iron metabolism is necessary to maintain normal physiological functions of the brain, but iron deposition is one of the causes of some neurodegenerative diseases. Increasing evidence shows that iron overload not only increases the risk of DM, but also contributes to the development of cognitive impairment...

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver...

The aim of the present study was to investigate the relationship between leptin and adiponectin gene polymorphisms, circulating levels of leptin and adiponectin, adiposity and clinical markers in patients with myelodysplastic syndrome (MDS). This cross-sectional study was conducted with 102 adults and elderly MDS patients and 102 age- and sex-matched controls. Clinical characteristics, comorbidities, anthropometric data, laboratory evaluation and genetic analysis (polymorphisms -2548G>A/rs7799039 of the LEP gene and +276G>T/rs1501299 of the ADIPOQ gene) were investigated...

BACKGROUND AND AIMS: One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion-dependent beta-thalassemia. METHODS: This descriptive cross-sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta-thalassemia major with frequent blood transfusions...

BACKGROUND: Hyperferritinemia is found in around 12 % of the general population. Analyzing the cause can be difficult. In case of doubt about the presence of major iron overload most guidelines advice to perform a MRI as a reliable non-invasive marker to measure liver iron concentration (LIC). In general, a LIC of ≥ 36 µmol/g is considered the be elevated however in hyperferritinemia associated with, for example, obesity or alcohol (over)consumption the LIC can be ≥ 36 µmol/g in abscence of major iron overload...

Diamond-Blackfan anemia (DBA) is one of the most common inherited causes of bone marrow failure in children. DBA typically presents with isolated erythroid hypoplasia and anemia in infants. Congenital anomalies are seen in 50% of the patients. Over time, many patients experience panhematopoietic defects resulting in immunodeficiency and multilineage hematopoietic cytopenias. Additionally, DBA is associated with increased risk of myelodysplastic syndrome, acute myeloid leukemia and solid organ cancers. As a prototypical ribosomopathy, DBA is caused by heterozygous loss-of-function mutations or deletions in over 20 ribosomal protein genes, with RPS19 being involved in 25% of patients...

Obesity is a complicated disease characterized by abundant fat accumulation. It is associated with cardiovascular disease. The current study aimed to appreciate the role of synthesized zinc oxide nanoparticles (ZnONPs) (18.72 nm in size) in curbing cardiovascular disease in an obesity model of a high fat/sucrose diet in male rats. For 16 weeks, 24 rats were fed a high-fat diet and a 25% sucrose solution to develop obesity, and after that, the rats were randomly allocated into four groups of rats. Group 1 served as the control group and consisted of normal, non-obese rats...

Studies have confirmed that hepatic iron overload is one of the important factors causing liver damage in the metabolic syndrome (MS). As a special form of autophagy, ferritinophagy is involved in the regulation of iron metabolism. Our previous studies have shown that chronic intermittent hypobaric hypoxia (CIHH) can improve the iron metabolism disorder. The aim of this study was to investigate how CIHH improves liver damage through ferritinophagy in MS rats. Male Sprague-Dawley rats aged 8-10 weeks were randomly divided into four groups: control (CON), CIHH (exposed to hypoxia at a simulated altitude of 5000 m for 28 days, 6 h daily), MS model (induced by a 16-week high-fat diet and 10% fructose water feeding), and MS + CIHH (exposed to CIHH after a 16-week MS inducement) groups...

Iron, as an essential trace element for the organism, is vital for maintaining the organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis is a novel form of programmed cell death distinguished by iron overload and lipid peroxidation, which is unique from autophagy, apoptosis and necrosis, more and more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis is associated with the development of female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), ovarian cancer (OC), preeclampsia (PE) and spontaneous abortion (SA)...

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Iron overload disorders can present as non-specific symptoms and develop gradually but, if untreated, can be very fatal. The common causes include multiple blood transfusions for chronic anemia and increased iron absorption, including hereditary hemochromatosis (HH). HH is one of the common causes of iron overload disorders and usually presents with liver cirrhosis in a setting of significantly elevated ferritin and elevated transferrin saturation. Alcoholic hepatitis is a clinical syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol...