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Genetic Haemochromatosis

Eva Rombout-Sestrienkova, Marian G J van Kraaij, Ger H Koek
A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In general, therapy is based on the removal of excess body iron, for which ferritin levels are used to monitor the effectiveness of treatment. For many decades phlebotomy has been widely accepted as the standard treatment...
October 10, 2016: British Journal of Haematology
Ulrike Manz
OBJECTIVE: The objective of this study is to explore the discriminatory impacts of genetic diagnosis for people living with the chronic illness of hereditary haemochromatosis in Germany. METHODS: Semi-structured interviews with 15 patients; all had tested positive for a genetic mutation associated with haemochromatosis and already displayed symptoms of the disease. Inductive approach, with interviews collaboratively interpreted by the research group in a vertical and horizontal analysis informed by a multi-person perspective...
May 12, 2016: Chronic Illness
Lise Fischer Henriksen, Anne-Sofie Petri, Hans Carl Hasselbalch, Jørgen Kim Kanters, Christina Ellervik
The prolongation of cardiac repolarization (QT interval) has been investigated in studies of patients with secondary iron overload. However, no previous population-based study examining the effect of increased iron stores on QT interval prolongation has previously been undertaken. We tested the hypothesis that increased iron stores and haemochromatosis genotype (genetically increased iron stores) are associated with prolongation of the QT interval. We included 20 261 individuals from the Danish General Suburban Population Study and examined differences in QT interval according to ferritin concentration, transferrin saturation, iron concentration, transferrin concentration and haemochromatosis genotype (C282Y/C282Y)...
September 2016: British Journal of Haematology
Lawrie W Powell, Rebecca C Seckington, Yves Deugnier
Haemochromatosis is now known to be an iron-storage disease with genetic heterogeneity but with a final common metabolic pathway resulting in inappropriately low production of the hormone hepcidin. This leads to increase in intestinal absorption and deposition of excessive amounts of iron in parenchymal cells which in turn results in eventual tissue damage and organ failure. A clinical enigma has been the variable clinical expression with some patients presenting with hepatic cirrhosis at a young age and others almost asymptomatic for life...
August 13, 2016: Lancet
C Pelusi, D I Gasparini, N Bianchi, R Pasquali
Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies...
August 2016: Journal of Endocrinological Investigation
Yang-Fan Lv, Xian Chang, Rui-Xi Hua, Guang-Ning Yan, Gang Meng, Xiao-Yu Liao, Xi Zhang, Qiao-Nan Guo
To investigate the association between mutation of HFE (the principal pathogenic gene in hereditary haemochromatosis) and risk of cancer, we conducted a meta-analysis of all available case-control or cohort studies relating to two missense mutations, C282Y and H63D mutations. Eligible studies were identified by searching databases including PubMed, Embase and the ISI Web of Knowledge. Overall and subgroup analyses were performed and odds ratios (ORs) combined with 95% confidence intervals (CIs) were applied to evaluate the association between C282Y mutation, H63D mutation and cancer risk...
July 2016: Journal of Cellular and Molecular Medicine
Allard R J V Vossen, Lianne S M Boesten, Peter D Siersema, Ruud G L Nellen
The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection...
2016: Nederlands Tijdschrift Voor Geneeskunde
Gino Seravalle, Alberto Piperno, Raffaella Mariani, Irene Pelloni, Rita Facchetti, Raffaella Dell'Oro, Cesare Cuspidi, Giuseppe Mancia, Guido Grassi
AIMS: Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown. METHODS AND RESULTS: In 18 males with primary HH (age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy...
March 21, 2016: European Heart Journal
Stefano Gazzina, Enrico Premi, Isabella Zanella, Giorgio Biasiotto, Silvana Archetti, Maura Cosseddu, Elio Scarpini, Daniela Galimberti, Maria Serpente, Roberto Gasparotti, Alessandro Padovani, Barbara Borroni
INTRODUCTION: Brain iron homeostasis dysregulation has been widely related to neurodegeneration. In particular, human haemochromatosis protein (HFE) is involved in iron metabolism, and HFE H63D polymorphism has been related to the risk of amyotrophic lateral sclerosis and Alzheimer's disease. Recently, iron accumulation in the basal ganglia of frontotemporal lobar degeneration (FTLD) patients has been described. OBJECTIVE: To explore the relationship between HFE genetic variation and demographic, clinical and imaging characteristics in a large cohort of FTLD patients...
2016: Neuro-degenerative Diseases
Nora Christe, Christoph A Meier
The term male hypogonadism is defined as the failure to maintain physiological concentrations of testosterone, a physiological quantity of sperm or the combination of both. Aetiologically, androgen deficiency can originate from the testes (primary hypogonadism) or from the hypothalamic-pituitary regulation of the testicular function (secondary hypogonadism). The causes of hypogonadism are very diverse and may be genetically determined (e.g. Klinefelter's syndrome) or acquired (tumours, infections, haemochromatosis)...
2015: Swiss Medical Weekly
Pierre Brissot, Olivier Loréal
Body iron has a very close relationship with the liver. Physiologically, the liver synthesizes transferrin, in charge of blood iron transport; ceruloplasmin, acting through its ferroxidase activity; and hepcidin, the master regulator of systemic iron. It also stores iron inside ferritin and serves as an iron reservoir, both protecting the cell from free iron toxicity and ensuring iron delivery to the body whenever needed. The liver is first in line for receiving iron from the gut and the spleen, and is, therefore, highly exposed to iron overload when plasma iron is in excess, especially through its high affinity for plasma non-transferrin bound iron...
February 2016: Journal of Hepatology
Peter Bentley, Barbara Bell, John Olynyk
BACKGROUND: Therapeutic venesection is an established treatment for hereditary haemochromatosis. The C282Y homozygotes and C282Y/H63D compound heterozygotes are the most likely human haemochromatosis protein (HFE) variants to cause iron over-load. The principal indications for treatment include iron overload, which is detected through measurement of hepatic iron concentration or a liver biopsy, or suspected iron-overload on the basis of elevated serum ferritin levels. Venesection is not indicated for other HFE genetic variants or in patients with isolated hyperferritinaemia in the absence of the main HFE gene mutations...
August 2015: Australian Family Physician
Natalie Funakoshi, Iphigénie Chaze, Anne-Sophie Alary, Gaëlle Tachon, Séverine Cunat, Muriel Giansily-Blaizot, Michael Bismuth, Dominique Larrey, Georges-Philippe Pageaux, Jean-François Schved, Hélène Donnadieu-Rigole, Pierre Blanc, Patricia Aguilar-Martinez
BACKGROUND & AIMS: Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). METHODS: Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI...
May 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Barbara de Graaff, Amanda Neil, Kristy Sanderson, Lei Si, Kwang Chien Yee, Andrew J Palmer
BACKGROUND: Hereditary haemochromatosis (HH) is a common genetic condition amongst people of northern European heritage. HH is associated with increased iron absorption leading to parenchymal organ damage and multiple arthropathies. Early diagnosis and treatment prevents complications. Population screening may increase early diagnosis, but no programmes have been introduced internationally: a paucity of health economic data is often cited as a barrier. OBJECTIVE: To conduct a systematic review of all health economic studies in HH...
October 2015: Applied Health Economics and Health Policy
Clara Benedetta Conti, Alessandra Baccarin, Dario Conte, Mirella Fraquelli
Present case report refers to a 48-year-old man with genetic haemochromatosis (C282Y mut/mut) diagnosed at the age of 26. After aggressive iron depleting regimen carried out up to normalization of iron-related indexes, he received a maintenance regimen based on regular phlebotomies for about 20 years. In 2014, a marked reduction of both serum ferritin and transferrin saturation percent, without concomitant anaemia, was noted on two different occasions at 5-month interval. An obscure occult GI bleeding was suspected, but both upper and lower GI tract endoscopy were negative for abnormal findings, as also was a detailed abdominal US scan...
October 2015: Internal and Emergency Medicine
S-R Chen, L-Q Yang, Y-T Chong, Y-S Jie, Y-K Wu, J Yang, G-L Lin, X-H Li
Here we report the case of a 69-year-old Chinese Han woman who presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia and high transferrin saturation. Subsequent genetic analyses identified a novel heterozygous mutation (p.Cys326Phe) in the SLC40A1 gene. This is the first report regarding a SLC40A1 mutation in the Chinese Han population and provides novel clinical evidence for the importance of p.Cys326 in SLC40A1 gene function.
June 2015: Internal Medicine Journal
Catherine Ogilvie, Dairena Gaffney, Heather Murray, Andrew Kerry, Caroline Haig, Richard Spooner, Edward J Fitzsimons
AIMS: There is high prevalence of hereditary haemochromatosis (HH) in North European populations, yet the diagnosis is often delayed or missed in primary care. Primary care physicians frequently request serum ferritin (SF) estimation but appear uncertain as how to investigate patients with raised SF values. Our aim was to develop a laboratory algorithm with high predictive value for the diagnosis of HH in patients from primary care with raised SF values. METHODS: Transferrin saturation (Tsat) was measured on SF samples sent from primary care; 1657 male and 2077 female patients age ≥ 30 years with SF ≥ 200 μg/L...
March 2015: Journal of Clinical Pathology
Federica Sangiuolo, Ermanno Puxeddu, Gabriella Pezzuto, Francesco Cavalli, Giuliana Longo, Alessia Comandini, Donato Di Pierro, Marco Pallante, Gianluigi Sergiacomi, Giovanni Simonetti, Maurizio Zompatori, Augusto Orlandi, Andrea Magrini, Massimo Amicosante, Francesca Mariani, Monica Losi, Daniela Fraboni, Alberto Bisetti, Cesare Saltini
In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage. The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL). Haemosiderin was assessed by Perls' stain, BAL fluid malondialdehyde (MDA) by high-performance liquid chromatography, BAL cell iron-dependent oxygen radical generation by fluorimetry and the frequency of hereditary haemochromatosis HFE gene variants by reverse dot blot hybridisation...
February 2015: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Annick Vanclooster, David Cassiman, Werner Van Steenbergen, Dorine W Swinkels, Mirian C H Janssen, Joost P H Drenth, Bert Aertgeerts, Hub Wollersheim
BACKGROUND AND OBJECTIVES: Hereditary haemochromatosis (HH) is the most prevalent genetic liver disease, with an incidence of 1/200 to 1/400 in the Caucasian population. HH patients are treated by family physicians as well as different specialists. When left untreated or insufficiently treated, the complications can become life threatening. To support and evaluate qualitative care for HH, we evaluated and compared the available structured guidelines on screening, diagnosis and management of HH patients...
April 2015: Clinics and Research in Hepatology and Gastroenterology
Rune J Ulvik
The review deals with genetic, regulatory and clinical aspects of iron homeostasis and hereditary haemochromatosis. Haemochromatosis was first described in the second half of the 19th century as a clinical entity characterized by excessive iron overload in the liver. Later, increased absorption of iron from the diet was identified as the pathophysiological hallmark. In the 1970s genetic evidence emerged supporting the apparent inheritable feature of the disease. And finally in 1996 a new "haemochromatosis gene" called HFE was described which was mutated in about 85% of the patients...
2015: Journal of Trace Elements in Medicine and Biology
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