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Major histocompatibility complex
Published in Gabriel Virella, Medical Immunology, 2019
Ellen Klohe, Janardan P. Pandey
Hemochromatosis is a disorder that increases the risk of iron overload. Family studies in Caucasians of western European descent demonstrated autosomal recessive inheritance in linkage with HLA-A3. Decades later, the HFE gene was discovered in close proximity to HLA-A. A common mutation within the HFE gene prohibits β2-microglobulin from binding to the HFE α-chain. This disrupts the binding of HFE to the transferrin receptor and alters iron absorption pathways.
Non-viral liver disease
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
John ML Christie, Roger WG Chapman
Hereditary haemochromatosis is the most common genetic disease in people of North European descent, with a prevalence of 1/300.80 The disease is caused by excess iron deposition in multiple organs, with the liver affected predominantly. The disease is inherited in an autosomal recessive manner. The gene (named the HFE gene) was identified in 199681 and is found on the short arm of chromosome 6. Two mutations within the gene have been shown to be associated with the disease, with the commonest mutation being the substitution cys282tyr. Of patients with haemochromatosis, 85% are homozygote for this mutation.
Jaundice
Published in Louisa Baxter, Neel Sharma, Ian Mann, The Junior Doctor’s Guide to Gastroenterology, 2018
Louisa Baxter, Neel Sharma, Ian Mann, Ian Sanderson
This is useful if haemochromatosis is suspected. This is an autosomal recessive disorder of iron metabolism whereby increased amounts of iron absorbed from the intestine are deposited in the liver, heart and endocrine glands. It may be detected by abnormal LFTs, raised serum ferritin levels, raised serum iron levels, reduced total iron-binding capacity (TIBC) and a transferrin saturation of > 80%. A liver biopsy and HFE gene mutation testing are diagnostic.
Hereditary hemochromatosis: data from a single center Copenhagen cohort
Published in Scandinavian Journal of Gastroenterology, 2022
Rikke Therkildsen, Eva Efsen Dahl, Frank Vinholt Schiødt
Retrospectively, patients with HH, not previously diagnosed at other centers, from the years 2009 to 2020 were included. Diagnosis was based on genotype. Biochemical data symptoms and signs were recorded following systematic interviews at presentation by one of the authors of this manuscript. The HFE gene was analyzed at Rigshospitalet, Copenhagen, a national biochemical and genetic center. Patients were followed at the HH outpatient clinic at Bispebjerg Hospital, an urban area of Copenhagen. The population in the hospital recruitment area is approximately 270,000 people. Patients were primarily referred from the general practitioner, the blood banks, rheumatologists, fertility centers, or after family follow-up; however, referral patterns were not systematically recorded. A plan for phlebotomies was scheduled according to national guidelines [17]. Phlebotomies were performed weekly in the early years 2009–2012, and from 2013 every two weeks at the clinic by experienced nurses until ferritin was <100 ug/L. The every-two-week phlebotomy program was easier to comply with for the patients.
Arthropathy in hereditary haemochromatosis segregates with elevated erythrocyte mean corpuscular volume
Published in Scandinavian Journal of Rheumatology, 2021
A Rehman, GJ Carroll, LW Powell, LE Ramm, GA Ramm, JK Olynyk
Hereditary haemochromatosis (HH) is an iron overload disorder affecting 1 in 200 individuals of northern European descent (1), usually caused by a homozygous C282Y mutation in the HFE gene (2, 3). Up to 30% of individuals homozygous for C282Y may develop significant disease from iron overload, including HH-related arthropathy (4). HH arthropathy was first described by Schumacher in 1964 and affects up to 81% of subjects (5). It is a significant cause of morbidity, disability, and reduced quality of life (6). Classically, arthropathy affects the finger metacarpophalangeal (MCP) joints and other joints such as the hips, ankles, radiocarpal, elbow, shoulder, and knee joints, as well as the lumbar spine (7). It is unclear why arthropathy affects only a subset of people with HH, or whether it can be predicted.
Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform
Published in Expert Review of Hematology, 2018
Peter Valent, Reinhard Stauder, Igor Theurl, Klaus Geissler, Thamer Sliwa, Wolfgang R. Sperr, Peter Bettelheim, Heinz Sill, Michael Pfeilstöcker
A number of different genetic and epigenetic factors may predispose for iron overload [64–71]. The highlighting example is hereditary hemochromatosis where HFE gene mutations (like C282Y and H63D) are found. Whereas homozygous carriers usually develop overt hemochromatosis during their lifetime, the impact of heterozygosity on tissue iron overload (in otherwise healthy or chronically transfused patients) remains uncertain. So far, it cannot be ruled out that heterozygosity for HFE gene mutations can predispose for rapid iron overload in transfused MDS patients. Other gene products involved in iron metabolism and/or storage include, among others, ferroportin 1 (FPN1), hemojuvelin (HFE2), and hepcidin [65]. It has also been described that HFE gene polymorphisms (mutations) are frequently detected in patients with MDS although the overall incidence may not be higher than that found in the general (healthy) age-matched population [68–71]. Therefore, our expert group does not recommend to screen for HFE gene variants or other genetic or epigenetic variables (potentially predisposing for iron overload) in all patients with transfusion-dependent MDS. Rather, we recommend that these studies should be performed when (i) serum ferritin levels and iron-saturation are very high and cannot be explained by the transfusion burden or comorbidities, (ii) a very rapid increase in ferritin is seen during transfusion therapy, or (iii) familial hemochromatosis is found in the case history.