Iron Overload Is Rare in Patients Homozygous for the H63D Mutation

Kelley, Melissa; Joshi, N G; Xie, Yazhou; Borgaonkar, Mark

doi:10.1155/2014/468521

Cited by 39 publications

(41 citation statements)

References 23 publications

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“…Two other commonly encountered mutations of the HFE gene are H63D and S65C, which are often included in HFE genetic panels. However, patients with homozygous H63D or S65C mutations, or those with C282Y heterozygosity, do not generally develop clinically significant iron overload unless other external iron‐increasing factors are present . There remains ambiguity regarding C282Y/H63D heterozygosity and whether this can lead to overt iron overload; some studies have shown a high prevalence of increased iron levels but typically only when present with other comorbid factors including hepatic steatosis, diabetes or excess alcohol consumption .…”

Section: Genetic Testing For Hereditary Haemochromatosismentioning

confidence: 99%

“…Even in individuals with homozygous HFE C282Y mutations, development of clinical iron overload is rare, reported in 21–28% of men and 1·2–10% of women . Given the rarity of non‐ HFE ‐associated haemochromatosis, it is difficult to quantify the penetrance of these mutations, but some research suggests that they are similarly low . Because the penetrance of HH is low, population screening for mutations has never been routinely recommended .…”

Section: Genetic Testing For Hereditary Haemochromatosismentioning

confidence: 99%

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Diagnosis and management of hereditary haemochromatosis

et al. 2020

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Hereditary haemochromatosis, one of the most common genetic disorders in the United States, can produce systemic iron deposition leading to end-organ failure and death if untreated. The diagnosis of this condition can be challenging as elevated serum ferritin may be seen in a variety of conditions, including acute and chronic liver disease, a range of systemic inflammatory states, and both primary and secondary iron overload syndromes. Appropriate and timely diagnosis of haemochromatosis is paramount as simple interventions, such as phlebotomy, can prevent or reverse organ damage from iron overload. The recognition of other aetiologies of elevated ferritin is also vital to ensure that appropriate intervention is provided and phlebotomy only utilized in patients who require it. In this review, we summarize the existing data on the work up and management of hereditary haemochromatosis and present a practical algorithm for the diagnosis and management of this disease.

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Section: Genetic Testing For Hereditary Haemochromatosismentioning

confidence: 99%

Section: Genetic Testing For Hereditary Haemochromatosismentioning

confidence: 99%

Diagnosis and management of hereditary haemochromatosis

et al. 2020

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“…C282Y homozygosity is the predominant form associated with clinical symptoms in 80 to 92% of cases (Feder et al, 1996; Hanson et al, 2001; Aguilar‐Martinez et al, 2011). H63D is unlikely to produce hemochromatosis, even in homozygotes (Beutler, 2006; Adams, 2014; Kelley et al, 2014). Compound heterozygotes, C282Y/H63D, and simple heterozygotes of either mutation carry a very low risk of HH disease (Waalen et al, 2002; Gurrin et al, 2009).…”

mentioning

confidence: 99%

The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

Heath

Axton

McCullough

et al. 2016

American J Phys Anthropol

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ObjectivesThe C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution. Here we hypothesize that this new Neolithic diet, which originated in the sunny warm and dry climates of the Middle East, was carried by migrating farmers into the chilly and damp environments of Europe where iron is a critical micronutrient for effective thermoregulation. We argue that the C282Y allele was an adaptation to this novel environment.Materials and MethodsTo address our hypothesis, we compiled C282Y allele frequencies, known Neolithic sites in Europe and climatic data on temperature and rainfall for statistical analysis.ResultsOur findings indicate that the geographic cline for C282Y frequency in Europe increases as average temperatures decrease below 16°C, a critical threshold for thermoregulation, with rainy days intensifying the trend.DiscussionThe results indicate that the deleterious C282Y allele, responsible for most cases of hemochromatosis, may have evolved as a selective advantage to culture and climate during the European Neolithic. Am J Phys Anthropol 160:86–101, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

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“…. A study by Kelley et al on patients homozygote for H63D showed that though the mutation is associated with an elevated mean ferritin level, only 6.7% of the patients documented iron overload at follow‐up. An over view on genetics and clinical implications of HFE‐associated hereditary hemochromatosis by Emanuele et al reported that knowledge of HFE‐HH is essential so that one can identify individuals at risk and provide appropriate management of care and referral.…”

Section: Discussionmentioning

confidence: 99%