Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (699 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes and Eponymic Diseases, 2d ed)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Von Recklenhausen-Applebaum Disease; Diseases, Von Recklenhausen-Applebaum; Disease, Von Recklenhausen-Applebaum; Recklenhausen-Applebaum Diseases, Von; Recklenhausen-Applebaum Disease, Von; Von Recklenhausen Applebaum Disease; Von Recklenhausen-Applebaum Diseases; Bronze Diabetes.
Where it fits in the MeSH classification
- Broader topics
- Metal Metabolism, Inborn Errors; Iron Overload
- See also
- Hepcidins
Related concepts
- Hemosiderosis
- Liver Cirrhosis
- Diabetes Mellitus
Research landscape
PubMed indexes 8,410 records tagged with the MeSH heading “Hemochromatosis” (counts retrieved 2026-10-29). 516 of them (6.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 4,478 records.
Reviews account for 1,384 records (16.5%) and meta-analyses for 18. Randomized controlled trials number 24 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 4,478 |
| 2000-2009 | 2,195 |
| 2010-2019 | 1,221 |
| 2020 onward | 516 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,384 | 16.5% |
| Meta-analyses | 18 | 0.2% |
| Randomized controlled trials | 24 | 0.3% |
Method: PubMed query "Hemochromatosis"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Hepcidin and Iron in Health and Disease | 2023 | Review article Design not recorded in structured metadata | 341 | cc by PMID 35905974 · DOI · PMC9943683 |
| Iron Homeostasis in Health and Disease | 2016 | Review article Design not recorded in structured metadata | 237 | cc by PMID 26805813 · DOI · PMC4730371 |
| Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank | 2019 | Research article Design not recorded in structured metadata | 153 | cc by PMID 30651232 · DOI · PMC6334179 |
| Comparing the types of haemochromatosis- from genetics to clinics | 2026 | Review article Design not recorded in structured metadata | 3 | cc by PMID 41882292 · DOI · PMC13424879 |
Hepcidin and Iron in Health and Disease [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Hepcidin, the iron-regulatory hormone, determines plasma iron concentrations and total body iron content.
- Closing excerpt
- The development of hepcidin diagnostics and therapeutic agonists and antagonists should improve the treatment of iron disorders.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (99 words)
Hepcidin, the iron-regulatory hormone, determines plasma iron concentrations and total body iron content. Hepcidin, secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to plasma from intestinal iron absorption and from iron stores. Hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy. Hepcidin deficiency causes iron overload in hemochromatosis and anemias with ineffective erythropoiesis. Hepcidin excess causes iron-restrictive anemias including anemia of inflammation. The development of hepcidin diagnostics and therapeutic agonists and antagonists should improve the treatment of iron disorders.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35905974 · DOI · PMC9943683
Iron Homeostasis in Health and Disease [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Iron is required for the survival of most organisms, including bacteria, plants, and humans.
- Closing excerpt
- This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (126 words)
Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 26805813 · DOI · PMC4730371
Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank [3]
Abstract reading summary — source excerpts
- Opening excerpt
- ObjectiveTo compare prevalent and incident morbidity and mortality between those with the HFE p.
- Closing excerpt
- C282Y associated iron overload is preventable and treatable if intervention starts early, these findings justify re-examination of options for expanded early case ascertainment and screening.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (229 words)
ObjectiveTo compare prevalent and incident morbidity and mortality between those with the HFE p.C282Y genetic variant (responsible for most hereditary haemochromatosis type 1) and those with no p.C282Y mutations, in a large UK community sample of European descent.DesignCohort study.Setting22 centres across England, Scotland, and Wales in UK Biobank (2006-10).Participants451 243 volunteers of European descent aged 40 to 70 years, with a mean follow-up of seven years (maximum 9.4 years) through hospital inpatient diagnoses and death certification.Main outcome measureOdds ratios and Cox hazard ratios of disease rates between participants with and without the haemochromatosis mutations, adjusted for age, genotyping array type, and genetic principal components. The sexes were analysed separately as morbidity due to iron excess occurs later in women.ResultsOf 2890 participants homozygous for p.C282Y (0.6%, or 1 in 156), haemochromatosis was diagnosed in 21.7% (95% confidence interval 19.5% to 24.1%, 281/1294) of men and 9.8% (8.4% to 11.2%, 156/1596) of women by end of follow-up. p.C282Y homozygous men aged 40 to 70 had a higher prevalence of diagnosed haemochromatosis (odds ratio 411.1, 95% confidence interval 299.0 to 565.3, Pv 3.4%, PConclusionsIn a large community sample, HFE p.C282Y homozygosity was associated with substantial prevalent and incident clinically diagnosed morbidity in both men and women. As p.C282Y associated iron overload is preventable and treatable if intervention starts early, these findings justify re-examination of options for expanded early case ascertainment and screening.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30651232 · DOI · PMC6334179
Comparing the types of haemochromatosis- from genetics to clinics [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Haemochromatosis is a genetic disorder of iron homeostasis.
- Closing excerpt
- There are minimal to absent levels of hepcidin in HAMP-related haemochromatosis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (245 words)
Haemochromatosis is a genetic disorder of iron homeostasis. It can be caused by mutations in genes encoding the iron-regulatory hormone hepcidin (HAMP), and/or genes that regulate hepcidin expression (HFE, HJV, TFR2), or a gain-of-function mutation in the gene encoding hepcidin receptor ferroportin (FPN1/SLC40A1). HFE-related haemochromatosis is prevalent predominantly in individuals of northern European descent. These mutations result in dysregulated levels or activity of hepcidin, leading to high iron-saturation of transferrin followed by progressive liver iron accumulation in the absence of anaemia. To enable and enhance the understanding of haemochromatosis in both researchers and prospective medics, this review collates and discusses the genetic basis and consequent pathophysiology of the different types of haemochromatosis within a single, comparative review. The discussion is supported by figures and a summary table that compares the haemochromatosis types for prevalence, clinical manifestations, primary organs affected, iron-related biochemical parameters and mechanisms of iron loading. Also, gain-of-function ferroportin mutation is compared to ferroportin disease, which is a loss-of-function ferroportin mutation, and shows a tendency to anaemia. Essentially, HFE-related haemochromatosis (common type) and TFR2-related haemochromatosis (rare type) show late-onset, milder and gradual iron loading, and often involve liver and joint damage. In contrast, HJV- and HAMP-related haemochromatosis (rare types) show severe and rapid iron loading in the first three decades of life, with notable cardiac and endocrine complications. Hepcidin levels are more markedly decreased in HJV-related haemochromatosis compared to HFE and TFR2 types. There are minimal to absent levels of hepcidin in HAMP-related haemochromatosis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41882292 · DOI · PMC13424879
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Hyperferritinemia and inflammation [5]
- Research article Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment [6]
- Research article Haemochromatosis [7]
- Research article EASL clinical practice guidelines for HFE hemochromatosis [8]
- Research article HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology [9]
- Research article Hepcidin--a regulator of intestinal iron absorption and iron recycling by macrophages [10]
References
- Nemeth E, Ganz T. Hepcidin and Iron in Health and Disease. . 2023. PMID 35905974 · DOI · PMC9943683
- Gozzelino R, Arosio P. Iron Homeostasis in Health and Disease. . 2016. PMID 26805813 · DOI · PMC4730371
- Pilling LC, Tamosauskaite J, Jones G, Wood AR, Jones L, Kuo CL, et al.. Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. . 2019. PMID 30651232 · DOI · PMC6334179
- Srinivasamurthy P, Mehta KJ. Comparing the types of haemochromatosis- from genetics to clinics. . 2026. PMID 41882292 · DOI · PMC13424879
- Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017. PMID 28541437 · DOI · PMC5890889
- Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010. PMID 20542038 · DOI
- Brissot P, Pietrangelo A, Adams PC, de Graaff B, McLaren CE, Loréal O. Haemochromatosis. Nat Rev Dis Primers. 2018. PMID 29620054 · DOI · PMC7775623
- European Association For The Study Of The Liver. EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol. 2010. PMID 20471131 · DOI
- Hanson EH, Imperatore G, Burke W. HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology. Am J Epidemiol. 2001. PMID 11479183 · DOI
- Ganz T. Hepcidin--a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol. 2005. PMID 15737883 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.