Hb Monza: A novel extensive HBB duplication with preserved α-β subunit interaction and unstable hemoglobin phenotype.

Background: Unstable hemoglobins are caused by single amino acid substitutions in the HBB gene, often affecting key histidine residues, leading to protein destabilization and hemolytic crises. In contrast, long HBB variants, exceeding 20 bp, are rare and associated with a β-thalassemia phenotype due to disrupted α-β chain interactions. We describe a family wherein four of six members carry a novel 23-amino-acid in-frame duplication of HBB (c.

Reference Values of Ceruloplasmin across the Adult Age Range in a Large Italian Healthy Population.

Background: Ceruloplasmin (Cp) is the most important serum copper transport protein playing a key role in the binding of iron to transferrin. It is a positive acute-phase response protein and the first-level diagnostic marker for Wilson disease and aceruloplasminemia. However, standardization of Cp measurement has not been successful, and assay specific reference levels of Cp are required.

Haemochromatosis in children: A national retrospective cohort promoted by the A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica) study group.

Haemochromatosis (HC) encompasses a range of genetic disorders. HFE-HC is by far the most common in adults, while non-HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain-of-function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood.

A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1.

Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. We previously studied eleven healthy subjects from eight different families presenting with unexplained hyperferritinemia. Their findings suggested the existence of an autosomal-recessive disorder.

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD).

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture.

Hereditary Hyperferritinemia.

Ferritin is a ubiquitous protein that is present in most tissues as a cytosolic protein. The major and common role of ferritin is to bind Fe, oxidize it and sequester it in a safe form in the cell, and to release iron according to cellular needs. Ferritin is also present at a considerably low proportion in normal mammalian sera and is relatively iron poor compared to tissues.

Possible Use of Minocycline in Adjunction to Intranasal Esketamine for the Management of Difficult to Treat Depression following Extensive Pharmacogenomic Testing: Two Case Reports.

The advent of intra-nasal esketamine (ESK), one of the first so called , promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of (DTD) than to TRD.

Intravenous iron therapy improves the hypercapnic ventilatory response and sleep disordered breathing in chronic heart failure.

Aims: Intravenous iron therapy can improve symptoms in patients with heart failure, anaemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns.

Methods And Results: Patients with heart failure, reduced left ventricular ejection fraction, anaemia (haemoglobin <13 g/dl in men; <12 g/dl in women) and iron deficiency (ferritin <100 or 100-299 μg/L with transferrin saturation <20%) were 2:1 randomized to patient-tailored intravenous ferric carboxymaltose dose or placebo.

Rhabdomyolysis after Intravenous Ferric Gluconate: A Case Report.

Unlabelled: Patients with severe iron deficiency, malabsorption or intolerance to oral iron are frequently treated with intravenous iron replacement. We report the case of a 42-year-old woman with non-erosive oligoarticular arthritis with antiparietal cell antibodies and iron deficiency anemia secondary to menorrhagia and unresponsive to oral iron preparations. She was treated with an intravenous infusion of ferric gluconate.

Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy.

Unlabelled: Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies.

Thalassaemia is paradoxically associated with a reduced risk of in-hospital complications and mortality in COVID-19: Data from an international registry.

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.

Iron-mediated tissue damage in acquired ineffective erythropoiesis disease: It's more a matter of burden or more of exposure to toxic iron form?

Iron is essential in cellular life, however, when in excess, it favors the production of reactive oxygen species (ROS) that, when overwhelm the physiological cellular antioxidant system, produce an oxidative stress state leading to cellular damages and organ failure. What is not yet completely clear is whether the damage is related more to the amount of iron or to the duration of exposure to ROS. Various cellular pathways are sensitive to the detrimental action of ROS in a non-dose-dependent manner.

New Mutations in and Genes Causing Non -Related Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) is an iron metabolism disease clinically characterized by excessive iron deposition in parenchymal organs such as liver, heart, pancreas, and joints. It is caused by mutations in at least five different genes. HFE hemochromatosis is the most common type of hemochromatosis, while non-HFE related hemochromatosis are rare cases.

Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia.

Background: Several inherited diseases cause hyperferritinemia with or without iron overload. Differential diagnosis is complex and requires an extensive work-up. Currently, a clinical-guided approach to genetic tests is performed based on gene-by-gene sequencing.

The use of esketamine in comorbid treatment resistant depression and obsessive compulsive disorder following extensive pharmacogenomic testing: a case report.

Background: Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive-compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration.

Prolonged exposure to welding fumes as a novel cause of systemic iron overload.

Background & Aims: Inhalation of welding fume may cause pulmonary disease known as welder's lung. At our centre we came across a number of welders with systemic iron overload and prolonged occupational history and we aimed at characterizing this novel clinical form of iron overload.

Methods: After exclusion of other known causes of iron overload, 20 welders were fully evaluated for working history, hepatic, metabolic and iron status.

A Putative Modifier of Hemochromatosis.

HFE-related hereditary hemochromatosis (HH) is characterized by marked phenotypic heterogeneity. Homozygosity for p.C282Y is a low penetrance genotype suggesting that the HFE-HH is a multifactorial disease resulting from a complex interaction involving a major gene defect, genetic background and environmental factors.

Inherited iron overload disorders.

Hereditary iron overload includes several disorders characterized by iron accumulation in tissues, organs, or even single cells or subcellular compartments. They are determined by mutations in genes directly involved in hepcidin regulation, cellular iron uptake, management and export, iron transport and storage. Systemic forms are characterized by increased serum ferritin with or without high transferrin saturation, and with or without functional iron deficient anemia.