Hemochromatosis, also known as siderosis, is a disease caused by excessive iron deposition in human organs and tissues, resulting from iron metabolism disorders. It is clinically characterized by skin pigmentation (bronze color), liver cirrhosis, diabetes, weakness, and fatigue. Additional symptoms may include arthritis, hypothyroidism, heart failure, and sexual hypofunction. Clinical manifestations can vary from person to person, with a few patients showing no clinical manifestations, which makes the diagnosis difficult for clinicians. In this case report, we described hereditary hemochromatosis related to a mutation in the HAMP gene in Fuyang City, China, as a reference for clinicians. Hereditary hemochromatosis is rarely reported in China. Clinicians in China have relatively insufficient knowledge of this disease, which leads to frequent misdiagnosis. In this case report, we describe hereditary hemochromatosis related to HAMP gene mutation in Fuyang City, China, for the clinician\'s reference.

UNASSIGNED: Many studies have pointed out that iron overload in the body is a risk factor for coronary atherosclerosis (AS), while there are also studies that show that iron deficiency is associated with coronary AS. There is still no consensus on how iron metabolism affects coronary artery disease (CAD). This study aimed to analyze the relationship between iron metabolism indexes and CAD, investigate the diagnostic value of soluble transferrin receptor (sTfR) in suspected CAD, and establish a diagnostic model.
UNASSIGNED: This was a retrospective study. A total of 268 people with CAD-like symptoms who underwent coronary angiography in the Department of Cardiovascular Medicine, The Second Affiliated Hospital of Anhui Medical University from September 2022 to May 2023 without other chronic diseases or related medication history were included in the study and formed a continuous series including 188 CAD patients and 80 control subjects. Each iron metabolism index was divided into a grade variable according to tertile. The comparison of CAD morbidity between the tertiles and nonlinear correlation test was conducted to investigate the relationship between iron metabolism indexes and CAD risk. We used restricted cubic spline (RCS) to plot the relationship curve between sTfR and CAD risk and to determine the sTfR value corresponding to the minimal odds, according to which we divided the total sample into the \"sTfR low level\" subgroup and the \"sTfR high level\" subgroup. Logistic regression analyses were used to establish diagnostic models in both subgroups. The diagnostic efficiency of the indexes and models was compared by receiver operating characteristic (ROC) analysis.
UNASSIGNED: There is a \"J\" shape correlation between sTfR and CAD risk. Age/sTfR ratio [area under the curve (AUC) =0.690, 95% confidence interval (CI): 0.598-0.782, specificity 0.488 and sensitivity 0.842] has the best diagnostic efficiency in the \"sTfR low level\" subgroup. The diagnostic efficiency of sTfR (AUC =0.701, 95% CI: 0.598-0.803, specificity 0.541 and sensitivity 0.797) in the \"sTfR high level\" subgroup was higher than that of cardiac troponin I (cTnI) (AUC =0.674, 95% CI: 0.564-0.784, specificity 0.719 and sensitivity 0.653). The specific diagnostic methods were as follows: (I) When sTfR ≤1.087 mg/L, calculate the age/sTfR ratio, which indicates the diagnosis of CAD when the result is >58.595; (II) We can directly make a preliminary clinical diagnosis of CAD when sTfR >1.205 mg/L. Except for the above 2 cases, we can initially rule out a diagnosis of CAD.
UNASSIGNED: The iron metabolism index sTfR correlates with CAD morbidity in a \"J\" shape. With superior diagnostic efficacy than cTnI, sTfR can assist in diagnosing CAD in patients with CAD-like symptoms. In addition, sTfR can provide guidance for the management of body iron levels in CAD patients.

Iron uptake, transport, and storage require the involvement of several proteins, including ferroportin (fpn), the sole known iron efflux transporter. Due to its critical function fpn has been studied, particularly in humans. Here, we characterized the ferroportin gene in common carp (Cyprinus carpio L.) and performed RNA-seq analysis to evaluate its constitutive transcription levels across different tissues. Our results indicate that C. carpio possesses two functional fpns with distinct expression patterns, highlighting the potential for functional divergence and expression differentiation among fpns in this species.

Reduced red cell mass is a poor prognostic indicator in chronic kidney disease (CKD) patients. Whilst overt anaemia impacts on the quality of life of patients with CKD, lowered red cell mass may also compromise oxygen delivery to proximal tubular cells and contribute to progressive kidney injury. Epidemiological data from cats with CKD support this hypothesis although controlled interventional studies involving drugs that raise red cell mass in trials designed to test this hypothesis are lacking in both human and veterinary medicine. Recombinant analogues of erythropoietin (EPO) are currently standard of care for human CKD patients where low red cell mass impacts on their quality of life. Resistance to EPO is encountered in 20% to 40% of patients treated, probably due to functional iron deficiency, reflecting the difficulties of managing iron deficiency associated with the chronic inflammation of CKD. Similar issues are likely faced in managing anaemia in feline CKD although published data on the use of human EPO analogues are limited as such treatment in cats risks antibody formation resulting in red cell aplasia and transfusion dependency and so is reserved for late stage cases only. This article reviews the recent alternative therapeutic approach to increase red cell mass using HIF-prolyl hydroxylase inhibitors and explains their mode of action and theoretical advantages over EPO analogues in the context of iron metabolism. The results of human clinical trials and the potential benefit of adopting this approach in feline CKD patients are discussed.

BACKGROUND: Human hepcidin, produced by hepatocytes, regulates intestinal iron absorption, iron recycling by macrophages, and iron release from hepatic storage. Recent studies indicate that hepcidin deficiency is the underlying cause of the most known form of hereditary hemochromatosis.
METHODS: A 44-year-old Asian man who developed type 2 diabetes mellitus had elevated serum ferritin levels (10,191 ng/mL). Liver biopsy revealed remarkable iron deposition in the hepatocytes and relatively advanced fibrosis (F3). Chromosomal analysis confirmed the presence of transferrin receptor type 2 mutations (c.1100T>G, c.2008_9delAC, hereditary hemochromatosis type 3 analyzed by Kawabata). The patient received intravenous infusions of Laennec (672 mg/day, three times/week) or oral administration with Porcine (3.87 g/day) for 84 months as an alternative to repeated phlebotomy. At the end of the treatment period, serum ferritin level decreased to 428.4 ng/mL (below the baseline level of 536.8 ng/mL). Hemoglobin A1c levels also improved after treatment with the same or lower dose of insulin (8.8% before versus 6.8% after). Plural liver biopsies revealed remarkable improvements in the grade of iron deposition and fibrosis (F3 before versus F1 after) of the liver tissue.
CONCLUSIONS: The discovery of hepcidin and its role in iron metabolism could lead to novel therapies for hereditary hemochromatosis. Laennec (parenteral) and Porcine (oral), which act as hepcidin inducers, actually improved iron overload in this hereditary hemochromatosis patient, without utilizing sequential phlebotomy. This suggests the possibility of not only improving the prognosis of hereditary hemochromatosis (types 1, 2, and 3) but also ameliorating complications, such as type 2 diabetes, liver fibrosis, and hypogonadism. Laennec and Porcine can completely replace continuous venesection in patients with venesection and may improve other iron-overloading disorders caused by hepcidin deficiency.

UNASSIGNED: Red cell pyruvate kinase deficiency (PKD) is a defect of glycolysis causing congenital non-spherocytic hemolytic anemia. PKD is transmitted as an autosomal recessive trait. The clinical features of PKD are highly variable, from mild to life-threatening anemia which can lead to death in the neonatal period. Most patients with PKD must receive regular transfusions in early childhood and as a consequence suffer from iron overloading.
UNASSIGNED: Here, we report a Polish family with life-threatening hemolytic anemia of unknown etiology. Whole exome sequencing identified two heterozygous mutations, c.1529 G > A (p.R510Q) and c.1495 T > C (p.S499P) in the PKLR gene. Molecular modeling showed that the both PKLR mutations are responsible for major disturbance of the protein structure and functioning. Despite frequent transfusions the patients do not show any signs of iron overload and hepcidin, a major regulator of iron uptake, is undetectable in their serum. The patients were homozygous for the rs855791 variant of the TMPRSS6 gene which has earlier been shown to down-regulate iron absorption and accumulation.
UNASSIGNED: The lack of iron overload despite a reduced level of hepcidin in two transfusion-dependent PKD patients suggests the existence of a hepcidin-independent mechanism of iron regulation preventing iron overloading.

Among the various pathologies of the oral cavity, the formation of \"unsightly black spots\" on the surface of the tooth, universally known as Black Stain (BS) has recently been acquiring more interest. Usually BS is typically found in individuals in prepubertal age, even though it has been identified in adults associated with microbial exchange and / or with iron metabolism disorders. Microbial exchange concerns the possible exchange of bacteria between family members which can take place directly, through effusions, or indirectly, through brushes, cutlery or glasses. For this reason, it is recommended that toothbrushes of family members not be left damp and in contact with each other. The bathroom, being a warm-humid environment, is in fact an optimal habitat for microbial proliferation. Of specific importance in BS is the accumulation of iron in tissues and secretions which, together with chromogenic bacteria, are the primary cause of this pathology. In fact, among the metabolic products synthesized by bacteria in the oral cavity, hydrogen sulfide is of considerable interest, since upon reacting with iron available in saliva, in pathological conditions (iron metabolism disorders), it forms black precipitates consisting of ferric sulfide. These precipitates bind to the surface of the teeth, tending to form a stria that usually follows the contour of the gingiva, with an unsightly and variable chromatic intensity. In physiological situations, iron homeostasis is defined as the state of equilibrium between iron present in tissues and in secretions and that which is present in the circulation. Instead, in pathological conditions, defined as iron metabolism disorders, there is an accumulation of iron in tissues and secretions and a lack of it in the circulation. It is also important to remember that subjects affected by BS are more protected from carious processes than healthy subjects, probably due to a significant predominance of chromogenic bacteria compared to those responsible for caries. It should also be remembered that in young subjects BS tends to regress with pubertal development and the transition to adult life. In any case, using common professional hygiene procedures, it is possible to remove BS as well as plaque and tartar deposits. In particular, with ultrasonic scalers, polishing pastes and powders carried by air and water jets, the surfaces of the teeth can be restored to their natural healthy state. All the techniques for removing the precipitates, are not enough however, to fix and permanently eradicate their appearance, as these precipitates last only for short periods and recur very frequently. Due to the frequent recurrences, new oral microbiota control therapies are emerging; among these the use of lactoferrin (Lf) in the dental field and particularly in the treatment of BS appears to be very promising. Taken togheter, here the effect of Lf in subjects affected by BS has been investigated.

Hemochromatosis is an autosomal recessive genetic disorder resulting in increased intestinal absorption of iron and eventually to iron overload. The onset of symptoms is usually seen around 40 years of age. Iron overload causes tissue damage in liver, pancreas, skin, joints, heart, and gonads. Approximately 50% of patients diagnosed with hemochromatosis will have either type 1 or type 2 diabetes mellitus (DM) because of selective beta-cell damage due to iron overload and leads to impaired insulin synthesis, release, and insulin resistance. Early diagnosis and treatment of hemochromatosis prevents the development of diabetes. We present a case in a 48-year-old male with a history of DM for 6 months and skin pigmentation over face for 1 year.

Wilson\'s disease (WD) is an autosomal genetic disease. In the present study, the patient was a 35-year-old woman who exhibited drinking bucking (bulbar paralysis) and dysphagia for a period of nine years. Genetic analysis of the patient identified the Thr935Met and Pro992Leu mutations, which lead to copper metabolism discharge barriers. Moreover, magnetic resonance imaging revealed a susceptibility-weighted imaging (SWI) hyperintense area in the bilateral substantia nigra and lenticular nuclei. These SWI observations indicated that \'mineral deposits\' were present. The present case demonstrates that the SWI hyperintense area in the bilateral lenticular nuclei, substantia nigra and red nucleus combined with the patient\'s symptoms indicated that there is a possibility to diagnose WD when it is not detected by genetic analysis. In addition, it demonstrates that systemic mineral removal treatment (including manganese, iron and copper) may be successful for the initial treatment of WD.

BACKGROUND: Although the comorbidity of migraine and restless legs syndrome (RLS) has been well-documented, the association between RLS and migraine frequency has yet to be elucidated. The present study aims to evaluate the prevalence of RLS among individuals who experience low-frequency, high-frequency, or chronic migraine presenting with and without aura.
METHODS: We conducted a cross-sectional, case-controlled study involving 505 participants receiving outpatient headache treatment. Standardized questionnaires were administered to collect information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were categorized into low-frequency (1-8/month), high-frequency (9-14/month), and chronic (≥15/month) headache groups. RLS was diagnosed according to the criteria outlined by the International RLS Study Group (IRLSSG). The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality and identify symptoms of anxiety and depression. Associations between migraine frequency and RLS prevalence were investigated using multivariate linear and logistic regression.
RESULTS: Univariate analysis revealed an effect of migraine frequency on RLS prevalence (p = 0.026), though this effect did not persist following adjustment for baseline characteristics (p = 0.256). The trend was robust in patients whose migraines presented with auras (p univariate = 0.002; p multivariate = 0.043) but not in those without auras (p univariate and p multivariate > 0.05). Higher anxiety [odds ratio (OR) = 1.18, p = 0.019] and sleep disturbance (OR = 1.17, p = 0.023) scores were associated with higher RLS prevalence.
CONCLUSIONS: Higher migraine frequency correlates with a higher prevalence of RLS, particularly among patients with auras.