Hemochromatosis Patients Research Articles

8283 Diabetes Mellitus in Patients with Hemochromatosis- A Diagnostic and Therapeutic Challenge

Abstract Disclosure: U. Rafat: None. M. Siddiqui: None. J.L. Gilden: Other; Self; Novartis Pharmaceuticals. A. Moid: Other; Self; Novartis Pharmaceuticals. Background: Primary Hemochromatosis is a genetic condition most commonly due to two sets of mutations in the Human homeostatic iron regular Protein (HFE) gene. HFE modulates the expression of hepcidin, which regulates intestinal iron absorption, plasma iron concentration and distribution of iron in tissues. Hemochromatosis patients are at high risk for developing diabetes mellitus (DM) due to iron overload in the pancreas with damage to Beta cells and impaired insulin secretory capacity. Hemochromatosis is often called Bronze Diabetes due to brown discoloration of the skin from accumulation of iron, and is characterized by hepatic fibrosis, fatigue, arthralgias, cirrhosis, DM, arthropathy, pigmentation and cardiomyopathy. Case: We present a Caucasian male with homozygous hereditary hemochromatosis, diagnosed by liver biopsy at age 40 due to transaminitis and Ferritin level of 1500 ng/mL and Genetic testing- 2 copies of HFE gene pathogenic variant (C282Y). He was later diagnosed with DM age 51, started on Metformin and referred to Endocrine clinic with abdominal bloating, and polyarticular arthralgias. Physical exam=Vital Signs normal (WT. 231lbs, BMI 34), with splenomegaly, but normal musculoskeletal exam and skin without bronze discoloration. Both parents had T2DM. Lab- Hb a1c 8.7% (0.0-5.6), Iron saturation 71% (10-50), Ferritin 66.3 ng/mL (26-388), C-Peptide 3.30 ng/ml (0.81-3.85), with glucose level of 119 mg/dL, and negative IA-2 <5.4 U/mL, negative Islet cell antibody, GAD 65 <5 IU/mL (nl <5), Insulin Autoantibody <0.4 U/mL (nl <0.4), and Zinc Transporter 8 antibodies <10 U/mL (nl <15). Liver tests- AST 39 U/L(10-37), ALT 77 U/L (10-65), ALP 89 U/L (45-117), total bilirubin 1.1 mg/dL(0.2-1.2). Hormonal evaluation included TSH 1.2 uIU/mL (0.55-4.78), ACTH 19 pg/mL (0-47), AM Cortisol 16.28 ug/d (5.30-22.50) IGF1 158 ng/mL (50-317) FSH 9.6 mIU/mL(l.40-18.10), LH 5.09 mIU/mL (1.50-9.30), Prolactin 7.40 ng/mL(2.10-17.70), total testosterone 374 ng/dL(250-1100), free testosterone 66.2 pg/mL (35.0-155.0). Echocardiogram-left ventricular hypertrophy and thick right ventricular wall with concerns for iron overload. Hba1c improved to 6.6% on Metformin. Fructosamine 351umol/L (151-300). In the absence of advanced cardiac, hepatic and other organ involvement, and presence of elevated C-peptide and high BMI, this patient is being managed as T2DM, with low threshold to initiate insulin therapy considering possibility of concomitant Bronze DM. Conclusion: It is important to determine type of DM, so appropriate management options can be devised. While insulin is recommended for management in Bronze Diabetes, insulin sensitizers, such as metformin and/or GLP 1 agonists can be used in type 2 DM. One must also consider therapy based upon the risk of cancer and acute pancreatitis in the setting of pancreatic iron overload, when considering antihyperglycemic therapies. Presentation: 6/2/2024

Hemochromatosis - too much iron

Hemochromatosis is a disorder of genetic origin which affects iron hemostasis, resulting in an increased transferrin saturation, hyperferritinemia and parenchymal iron overload.Recently, a new system for the classification of hemochromatosis has been proposed, wherein patients are separated into 4 groups, based on the disease affected iron regulatory genes. Excess iron and increased transferrin saturation results in the formation of non-transferrin bound iron which leads to tissue damage. Hemochromatosis is a common genetic disease, but screening of the general population is not routinely recommended. In order to provide ideal care for hemochromatosis patients, it is crucial to delineate hemochromatosis from other causes of hyperferritinemia, which is a common finding in patients with metabolic disorders. This article summarizes the diagnostic algorithm for hemochromatosis. Furthermore, recommendations for optimal care - including targets for phlebotomy - are discussed.

Tumour stemness and poor clinical outcomes in haemochromatosis patients with hepatocellular carcinoma

AimsPatients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is...

Iron Metabolism, Calcium, Magnesium and Trace Elements: A Review.

Iron (Fe) is fundamental to life on earth. In the human body, it is both essential and harmful if above threshold. A similar balance applies to other elements: calcium (Ca), magnesium (Mg), and trace elements including copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), mercury (Hg), and nickel (Ni). These elements share some proteins involved in the absorption and transport of Fe. Cu and Cd can inhibit Fe absorption, while excess of Fe may antagonize Cu metabolism and reduce ceruloplasmin (Cp). Excessive Fe can hinder Zn absorption and transferrin (Trf) can bind to both Zn and Ni. Ca is able to inhibit the divalent metal transporter 1 (DMT1) in a dose-dependent manner to reduce Fe absorption and low Mg concentrations can exacerbate Fe deficiency. Pb competitively inhibits Fe distribution and elevated Cd absorption reduces Fe uptake. Exposure to Hg is associated with higher ferritin concentrations and Ni alters intracellular Fe metabolism. Fe removal by phlebotomy in hemochromatosis patients has shown to increase the levels of Cd and Pb and alter the concentrations of trace elements in some types of anemia. Yet, the effects of chronic exposure of most trace elements remain poorly understood.

Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption

Introduction: Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients. Methods: An LC-MS/MS-based method was performed to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 h after an iron-rich meal in HH patients. Results: Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal. Discussion: The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal, but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism.

Penetrance, cancer incidence and survival in HFE haemochromatosis-A population-based cohort study.

Haemochromatosis is characterized by progressive iron overload affecting the liver and can cause cirrhosis and hepatocellular carcinoma. Most haemochromatosis patients are homozygous for p.C282Y in HFE, but only a minority of individuals with this genotype will develop the disease. The aim was to assess the penetrance of iron overload, fibrosis, hepatocellular carcinoma and life expectancy. A total of 8839 individuals from the Austrian region of Tyrol were genotyped for the p.C282Y variant between 1997 and 2021. Demographic, laboratory parameters and causes of death were assessed from health records. Penetrance, survival, and cancer incidence were ascertained from diagnosed cases, insurance- and cancer registry data. Outcomes were compared with a propensity score-matched control population. Median age at diagnosis in 542 p.C282Y homozygous individuals was 47.8 years (64% male). At genotyping, the prevalence of iron overload was 55%. The cumulative penetrance of haemochromatosis defined as the presence of provisional iron overload was 24.2% in males and 10.5% in females aged 60 years or younger. Among p.C282Y homozygotes of the same ages, the cumulative proportion of individuals without fibrosis (FIB-4 score < 1.3) was 92.8% in males and 96.7% in females. Median life expectancy was reduced by 6.8 years in individuals homozygous for p.C282Y when compared with population-matched controls (p = .001). Hepatocellular carcinoma incidence was not significantly higher in p.C282Y homozygotes than in controls matched for age and sex. Reduced survival and the observed age-dependent increase in penetrance among p.C282Y homozygotes call for earlier diagnosis of haemochromatosis to prevent complications.

Self-Sustainability with Therapeutic Phlebotomy, a Solution to the National Blood Crisis?

CONCLUSION Hereditary hemochromatosis (HH) is a genetic condition associated with iron overload in the human body. The mainstay of treatment remains therapeutic phlebotomy. On August 1st, 2022, the American Red Cross approved using blood obtained from therapeutic phlebotomy for transfusion. While normal individuals can donate blood only as often as once in 56 days, individuals with HH can have phlebotomy as often as once weekly. Utilizing the blood collected from these patients could be a significant resource to mitigate the shortage of blood needed for transfusion. We aimed to quantify the number of units of blood removed by therapeutic phlebotomy from individuals with HH and assess its potential contribution to total units of blood required in a community hospital for two years (2021 and 2022). We retrospectively reviewed electronic medical records of adult individuals who underwent therapeutic phlebotomy at Saint Vincent Hospital between January 1, 2021, and December 31, 2022. Patients with hereditary hemochromatosis were identified based on a positive genetic test for HFE gene mutations. We collected data including gender, race, age at diagnosis, and the number of units of blood removed from patients during the study period. The total number of units transfused in the in-patient care services and operating room was obtained. A descriptive statistic was performed using R version 4.2.2 statistics software. A total of 112 patients received therapeutic phlebotomy over two years (2021 and 2022) of whom 65% (N=73) had a diagnosis of HH. A majority of the patients were males (60%, 44/73) and were non-Hispanic/Latino (85%, 62/73). The mean age at diagnosis of HH was 62 [standard deviation (SD): 17] years. The median number of units of blood removed by phlebotomy per patient with HH was 3 (2-5), the annual distribution is as displayed in Table 1. A total of 504 units of whole blood was removed through therapeutic phlebotomy from 73 patients during the study period. The total requirement for blood transfusion across all the departments in the hospital was 6065 units (2,733 units in 2021 and 3,332 units in 2022). The total number of units removed through therapeutic phlebotomy in HH patients represented 8.31% (504/6065 Units) and 82.49% (504/611 Units) of total units of blood requirement for the entire hospital and operating room respectively (Table 2). The units of blood removed through therapeutic phlebotomy of patients with HH, could potentially help sustain 8.31% of total blood requirement of the hospital. Primarily, over 82% of the demand from the operating room could be fulfilled if the entirety of the blood from therapeutic phlebotomy were to be transfused. Overcoming technical challenges in utilizing the blood from therapeutic phlebotomy for transfusion in routine clinical practice could help mitigate the national blood crisis and aid in self-sustainability of blood products at a community level. Our study highlights the need for broader efforts to create awareness and incentivizing re-utilization of blood obtained from therapeutic phlebotomy.

Maternal and prenatal outcomes of hemochromatosis in pregnancy: A population-based study.

This retrospective study investigated the impact of hemochromatosis on maternal and perinatal outcomes among delivery hospitalizations in the United States between 2010 and 2019, revealing notable trends and associations. Utilizing data from over 36 million delivery hospitalizations, we conducted a comprehensive analysis, focusing on maternal complications, perinatal outcomes, and healthcare utilization among women with hemochromatosis compared to those without. Women with hemochromatosis exhibited a longer length of hospital stay (3.27±0.20 days vs. 2.64±0.04 days) and higher total hospital charges ($21,789.66 ± $1124.41vs. $17,751.63 ± $97.71) compared to those without the condition. There was a significant increase in the prevalence of hemochromatosis among delivery hospitalizations over the studied period, from 1.91 per 100,000 hospitalizations to 8.65 cases per 100,000 hospitalizations. Hemochromatosis patients demonstrated a higher prevalence of hypertensive disorders of pregnancy (aOR: 1.50, 95% CI: 1.03-2.19) and VTE(aOR: 20.35, 95% CI: 5.05-82.05).There were no statistically significant differences in rates of peripartum hemorrhage, C-section, preterm birth, fetal growth restriction, large for gestational age infants, and fetal death between the two groups. Our findings underscore higher hypertensive disorders of pregnancy and VTE among women with hemochromatosis, despite unaffected perinatal outcomes. An increasing trend in hemochromatosis prevalence highlights the need for targeted interventions and cost-effective management strategies. Future research is needed to explore potential racial disparities and understand the rising incidence of hemochromatosis among pregnant women.

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

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. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.

Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications.

Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity.

Haemochromatosis patients' research priorities: Towards an improved quality of life.

Chronic diseases are associated with a range of functional and psychosocial consequences that can adversely affect patients' quality of life (QoL). Haemochromatosis (HC) is a genetically heterogeneous disorder characterized by chronic iron overload that can ultimately lead to multiple organ dysfunction. Clinical diagnosis remains challenging due to the nonspecificity of symptoms and a lack of confirmatory genotyping in a substantial proportion of patients. Illness perception among HC patients has not been extensively investigated, lacking relevant information on how to improve their QoL. We present the results of the first worldwide survey conducted in nearly 1500 HC respondents, in which we collected essential demographic information and identified the aspects that concern HC patients the most. Out of all the participants, 45.3% (n = 676) voiced their concern about physical and psychological consequences such as HC-related arthropathies, which can ultimately affect their social functioning. A similar proportion of patients (n = 635, 42.5%) also consider that better-informed doctors are key for improved HC disease management. Taking a patient-centred approach, we expose differences in patients' disease perspective by social and economic influences. We identify potential targets to improve patients' health-related QoL and reflect on strategic measures to foster gender equity in access to health resources. Finally, we make a call for a highly coordinated effort across a range of public policy areas to empower participants in the HC research process and design. Nearly 1500 patients with hereditary HC responded to an anonymized online survey in which research and clinical priorities were addressed regarding this chronic and rare disease.

Hereditary Liver Diseases: Wilson's Disease and Hemochromatosis

Wilson's disease and HFE-hemochromatosis are autosomal-recessively inherited metabolic diseases of the liver. Copper overload in case of Wilson's disease and iron overload in case of hemochromatosis lead to organ damage of the liver and other organs. In order to diagnose these diseases at an early stage and introduce therapy, knowledge of the symptoms and diagnostic criteria of these diseases is important. Iron overload in hemochromatosis patients is treated with phlebotomies and copper overload in Wilson's disease patients with either chelating medications (D-penicillamine or trientine) or zinc salts. After introduction of lifelong therapy both diseases typically have a favorable disease course and further development of organ-damage can be prevented, especially with respect to liver-damage.

Type 1 Hemochromatosis: A Review of the History, Inheritance and Treatment of Iron Overload Disorder

Hereditary hemochromatosis (also known as type 1 hemochromatosis, iron overload disorder, or the Celtic Curse) is a genetic disorder characterized by an autosomal recessive inheritance pattern. This review project focused on gathering comprehensive data about the history, causes, inheritance, diagnosis, and treatment of iron overload disorder. Through such research, it was discovered that type 1 hemochromatosis may occur due to one of two nucleotide sequence changes (either the C282Y mutation or the H63D mutation) in the HFE gene, which codes for the construction of the homeostatic iron regulator protein and regulates production of the hormone hepcidin. As a result of these mutations, individuals affected by hemochromatosis have elevated iron levels and excess deposits of iron in tissues and organs. Such deposits may cause a variety of symptoms and complications, including fatigue, skin discoloration, heart failure, cirrhosis, liver cancer, and diabetes. Hemochromatosis is one of the most common genetic disorders in the world, affecting one in every three hundred individuals. The majority of hemochromatosis patients are of northern European descent. Currently, there is no cure for type 1 hemochromatosis; however, the primary treatment method for this disorder is phlebotomy. Due to the widespread prevalence of the disorder, researchers continue to explore experimental treatment methods, including gene therapy and iron chelation therapy.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

Comparison of low PSA results in a commutable EQA program

The RCPAQAP provides a Liquid Serum Chemistry Program sourced from consenting male and female haemochromatosis patients presenting for therapeutic venesection. Where possible, serum from individual male and female patients are pooled over successive collections. The option to report PSA and Free PSA was introduced in the 2022 program. Here we report on the performance at low PSA levels across 6 instruments from 4 vendors.

Comparison of low troponin I results in a commutable EQA program

The RCPAQAP provides a Liquid Serum Chemistry Program sourced from consenting male and female haemochromatosis patients presenting for therapeutic venesection. Where possible, serum from individual male and female patients are pooled over successive collections. The option to report Troponin I and T was introduced in the 2022 program. We sought to review the performance at low Troponin I levels across 10 instruments from five vendors, and Troponin T for four Roche instruments. Methods: The median results for each platform submitted by to 151 participating laboratories for the November 2022 survey were compared using RCPAQAP inhouse software. Results: The Troponin I Instrument medians for the male sample ranged from 2 to 6 ng/L, with an all-result median of 3ng/L (n=151). The female sample ranged from 2 to 11ng/L, with an all-result median of 4ng/L (n=151). The all results medians for the male and female samples were the same for Troponin T: 6ng/L (n=39), and only varied by +/-1ng/L across the five platforms. Discussion: While this study is limited, it does demonstrate comparable results at low levels across five major vendors. Differences in decision points currently in use may warrant review as recent studies on low levels of troponin may potentially change clinical management.

Abstract 14180: Characteristics and In-Hospital Outcomes of Haemochromatosis in Heart Failure

Introduction: Cardiovascular complications are the main contributors towards morbidity and mortality in hemochromatosis. Iron overload can cause arrhythmias and heart failure (HF). There is a paucity of data on haemochromatosis and the burden of HF and its sequalae. Hypothesis: To determine characteristics of HF patients with and without haemochromatosis, and in-hospital outcomes (mortality, length of stay (LOS), mechanical circulatory support, and cardiac transplantation). Methods: Patients with HF, with and without hemochromatosis, were identified from the Nationwide Inpatient Sample Database. Results: Between 2016-2019, 2,940 (0.06%) of 4,823,994 HF patients had hemochromatosis. The hemochromatosis cohort was younger (mean age, 68 vs 71 years), predominantly men (63% vs 52%), White (77% vs 64%), and had less cardiovascular comorbidity burden (coronary artery disease (41% vs 51%), atrial fibrillation (45% vs 46%), hypertension (20% vs 24%), hyperlipidaemia (44% vs 53%), diabetes (42% vs 49%) and obesity (18% vs 25%), compared with HF patients without hemochromatosis (p&lt;0.01 for all). However, hemochromatosis patients had a higher concomitant third degree atrio-ventricular block (1.2% vs 0.7%), ventricular tachycardia (7.8% vs 5.4%), ventricular fibrillation (0.5% vs 0.3%), chronic liver disease (24% vs 6%) and anemia (51% vs 37%) [p&lt;0.01]. The hemochromatosis patients had a higher mean LOS (6.1 vs 5.4 days, p&lt;0.01), need for mechanical circulatory support (0.9% vs 0.6%, p&lt;0.01) and cardiac transplantation (0.2% vs 0.1%, p&lt;0.01). Mortality (2.0% vs 2.7%, p=0.09) was comparable between the groups. Conclusion: Despite younger age and lower burden of cardiovascular comorbidities, patients with hemochromatosis had a higher burden of arrhythmias, need for mechanical circulatory support and cardiac transplantation and a higher LOS. This warrants the need to devise early management strategies for HF patients with hemochromatosis.

Current German Guidelines on Diagnosis and Treatment of Secondary Hemochromatosis in Patients with Congenital Anemias.

Adequate diagnosis and treatment of secondary hemochromatosis in patients with congenital anemias is important for reducing long-term mortality and morbidity as for improving patients' quality of life. Due to the strong migration movements during recent years, the number of patients in Germany suffering from hemoglobinopathies as some of the most relevant disorders in the context of iron overload (IOL) has increased enormously. Many of these patients had received inadequate medical care in their countries of origin prior to migration, including diagnosis and treatment of IOL. In parallel, various medical developments and achievements took place, including the expansion of stem cell transplant as curative therapeutic option and the introduction of gene therapy for patients with hemoglobinopathies. Diagnostic tools to assess both liver and heart IOL became available at more sites in Germany. Overall experience with iron elimination therapy either as monotherapy or as combination of different chelators increased. All these aspects were considered during revision of the consensus-based guideline on the diagnosis and treatment of secondary IOL in patients with congenital anemias (AWMF Reg. No. 025/029). Here, we briefly summarize the procedure for the revision of the guideline, provide a brief overview of innovations as compared to the previous version dated from 2015, and finally present the consensus recommendations adopted in the current version.

Left Ventricular Function and Iron Loading Status in a Tertiary Center Hemochromatosis Cohort-A Cardiac Magnetic Resonance Study.

Haemochromatosis (HCH), a common genetic disorder with variable penetrance, results in progressive but understudied iron overload. We prospectively evaluated organ iron loading and cardiac function in a tertiary center HCH cohort. 42 HCH patients (47 ± 14 years) and 36 controls underwent laboratory workup and cardiac magnetic resonance (CMR), including T1 and T2* mapping. Myocardial T2* (myoT2*), myocardial T1 (myoT1) and liver T2* (livT2*) were lower in patients compared to controls (33 ± 4 ms vs. 36 ± 3 ms [p = 0.004], 964 ± 33 ms vs. 979 ± 25 ms [p = 0.028] and 21 ± 10 ms vs. 30 ± 5 ms [p &lt; 0.001], respectively). MyoT2* did not reach the threshold of clinically significant iron overload (&lt;20 ms), in any of the patients. In 22 (52.4%) patients, at least one of the tissue parameters was reduced. Reduced myocardial T2* and/or T1 were found in 10 (23.8%) patients, including 4 pts with normal livT2*. LivT2* was reduced in 18 (42.9%) patients. MyoT1 and livT2* inversely correlated with ferritin (rs = -0.351 [p = 0.028] and rs = -0.602 [p &lt; 0.001], respectively). LivT2* by a dedicated sequence and livT2* by cardiac T2* mapping showed good agreement (ICC = 0.876 p &lt; 0.001). In contemporary hemochromatosis, significant myocardial iron overload is rare. Low myocardial T2* and/or T1 values may warrant closer follow-up for accelerated myocardial iron overload even in patients without overt liver overload. Cardiac T2* mapping sequence allows for liver screening at the time of CMR.

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.