Materiały źródłowe

• #1 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hereditary hemochromatosis is the most common autosomal recessive disorder in White populations, with a prevalence of 1 in 300 to 500 individuals. […] The prevalence of hemochromatosis is the same in Europe, Australia, and other Western countries, with excess in people of Celtic or Scandinavian origin. Hemochromatosis is less prevalent in patients of African descent. White individuals have a 6 times higher risk of developing the disease than Black individuals. […] In hemochromatosis, men are affected 2 to 3 times more often than women. The estimated ratio between men and women is 1.8:1 to 3:1. Women with hemochromatosis become symptomatic later in life than men due to the blood loss and consequent iron excretion associated with menstruation. The disease usually becomes apparent in men in the fifth decade; in women, it often presents in the sixth decade. […] Analyses of a p.C282Y homozygous genotypic subset have revealed the greatest morbidity is in those patients older than 60.

• #2 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Hereditary hemochromatosis is the most common inherited disorder among people of northern European ancestry. […] The United States, Europe, and Australia have a similar disease prevalence of one case per 200 to 400 people, with the highest prevalence in those of Irish and Scandinavian ancestry. […] Despite the high prevalence of the gene mutation, there is a low and variable clinical penetrance, with up to 25% of people with C282Y homozygosity being clinically asymptomatic. […] The clinical manifestations of iron overload typically develop in the 40s or 50s. […] The disease is equally prevalent in men and women. Women typically present later in life when they are postmenopausal, likely because of menstrual blood loss delaying the development of symptomatic iron overload. […] The incidence of hepatocellular carcinoma is 20 to 200 times higher in patients with hereditary hemochromatosis, especially those with higher than stage 3 fibrosis and cirrhosis.

• #3 Genetics of hereditary hemochromatosis | British Columbia Medical Journal

  https://bcmj.org/articles/genetics-hereditary-hemochromatosis

  Hereditary hemochromatosis is probably the most common inherited disorder of people of northern European ancestry. Prevalence is estimated at 1 in 200 to 1 in 400, with an even higher rate in Ireland. […] HHC is almost invariably an autosomal recessive condition. The prevalence is between 1 in 200 to 1 in 400 in people of northern European ancestry. An even higher prevalence likely occurs in Ireland and has been estimated as great as 1 in 64. […] Hemochromatosis is a common disorder, and between 1 in 200 to 1 in 400 persons of northern European ancestry is a C282Y homozygote. Among the Irish the rate of C282Y homozygosity is higher than 1 in 100. […] Because of the protean manifestations of hemochromatosis, it should be considered in any patient presenting with fatigue, arthritis, liver dysfunction, gonadal failure, diabetes mellitus, skin pigmentation, arrhythmias, or cardiac disorders.

• #4 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Prevalence of hereditary hemochromatosis in the United States is 1 case in 200-500 individuals. Most are of northern European origin. Frequency of the C282Y mutation is 5.4% and that of the H63D mutation is 13.5%. Prevalence of C282Y homozygosity has been estimated to be 0.26%, the H63D homozygosity was estimated to be 1.89%, and compound heterozygosity was estimated to be 1.97%. The carrier state is estimated to be approximately 10%. […] The worldwide frequency of the C282Y is about 1.9% and that of the H63D mutation is about 8.1%. Hemochromatosis has the same prevalence in Europe, Australia, and other Western countries, with the highest prevalence being noted in people of Celtic origin. Hemochromatosis is less common among patients of African descent. […] Marked geographical disparity in the distribution of the C282Y mutation has been noted. Non-HFE- associated hereditary hemochromatosis was found in Mediterranean countries.

• #5 Hemochromatosis

  https://mobile.fpnotebook.com/GI/HemeOnc/Hmchrmts.htm

  Hereditary Hemochromatosis is the most common inherited condition in those of northern european descent. […] Highest Prevalence is in Irish and Scandinavian descendents. […] Prevalence 1 per 200-400 in U.S., Europe, Australia. […] Homozygous C282Y Prevalence varies across ethnicity (rare in non-white patients). […] White: 4.4 per 1000. […] Hispanic: 0.27 per 1000. […] Black: 0.14 per 1000. […] Asian American: 0.001 per 1000. […] Typical manifestations of Iron Overload occur in ages 40 to 50 years. […] Women present at a later age than men (due to menstrual blood loss up to Menopause). […] Cirrhosis risk increases 9 fold for daily Alcohol intake of more than 60g or 4 drinks. […] Screening for Hemochromatosis is indicated in cases of generalized weakness, arthralgias, hepatomegaly, and elevated liver transaminases.

• #6 Hemochromatosis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Hemochromatosis_epidemiology_and_demographics

  Non-Hispanic whites 44000 cases in 100000. […] Native Americans 11000 cases in 100000. […] Hispanics 270 cases in 100000. […] Blacks 140 cases in 100000. […] Pacific Islanders cases 120 in 100000. […] Asians less then 1 case in 100000. […] The European countries with the highest prevalence include Ireland, France, and Denmark.

• #7 9 Imaging in hereditary haemochromatosis: establishing a local guideline for cardiac and hepatic surveillance | Heart

  https://heart.bmj.com/content/104/Suppl_7/A9.1

  Hereditary haemochromatosis (HH) is an autosomal recessive condition, most commonly caused by HFE gene mutations. The prevalence of HH in Ireland is 1 in 83 per head of population. […] There are no definitive guidelines in HH for the frequency of liver or cardiac imaging to assess for complications of iron overload. Our aim was to assess our patient cohort in order to establish a local guideline for interval surveillance. […] Ferritin level 500 at diagnosis is not associated with an increased risk for liver dysfunction and, therefore, interval for liver screening may be decreased to 18-monthly, yielding cost savings. Although numbers are small, there appears to be a correlation between high ferritin levels and cardiac structural abnormality. Therefore, we recommend that all patients undergo echocardiography at diagnosis and every 12 years thereafter.

• #8 Genetics of hereditary hemochromatosis | British Columbia Medical Journal

  https://bcmj.org/articles/genetics-hereditary-hemochromatosis

  Hereditary hemochromatosis is probably the most common inherited disorder of people of northern European ancestry. Prevalence is estimated at 1 in 200 to 1 in 400, with an even higher rate in Ireland. […] HHC is almost invariably an autosomal recessive condition. The prevalence is between 1 in 200 to 1 in 400 in people of northern European ancestry. An even higher prevalence likely occurs in Ireland and has been estimated as great as 1 in 64. […] Hemochromatosis is a common disorder, and between 1 in 200 to 1 in 400 persons of northern European ancestry is a C282Y homozygote. Among the Irish the rate of C282Y homozygosity is higher than 1 in 100. […] Because of the protean manifestations of hemochromatosis, it should be considered in any patient presenting with fatigue, arthritis, liver dysfunction, gonadal failure, diabetes mellitus, skin pigmentation, arrhythmias, or cardiac disorders.

• #9 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Prevalence of hereditary hemochromatosis in the United States is 1 case in 200-500 individuals. Most are of northern European origin. Frequency of the C282Y mutation is 5.4% and that of the H63D mutation is 13.5%. Prevalence of C282Y homozygosity has been estimated to be 0.26%, the H63D homozygosity was estimated to be 1.89%, and compound heterozygosity was estimated to be 1.97%. The carrier state is estimated to be approximately 10%. […] The worldwide frequency of the C282Y is about 1.9% and that of the H63D mutation is about 8.1%. Hemochromatosis has the same prevalence in Europe, Australia, and other Western countries, with the highest prevalence being noted in people of Celtic origin. Hemochromatosis is less common among patients of African descent. […] Marked geographical disparity in the distribution of the C282Y mutation has been noted. Non-HFE- associated hereditary hemochromatosis was found in Mediterranean countries.

• #10 Hemochromatosis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Hemochromatosis_epidemiology_and_demographics

  Hemochromatosis is one of the most common inheritable genetic defects. […] In 2016, the incidence of C282Y is estimated to be 5400 cases per 100,000. […] In 2016, the incidence of H63D is estimated to be 13500 cases per 100,000. […] In 2017, the prevalence of Hemochromatosis was estimated to be from 500 case in 100000 individuals. […] The carrier state is estimated to be approximately 10000 in 100000. […] Prevalence of hemochromatosis is 6 times higher in white persons than in black persons. […] C282Y homozygotes account for 82-90% of clinical diagnoses of hereditary hemochromatosis among persons of northern European descent. […] Irish have highest prevalence of hemochromatosis. […] In 2005, estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites than in Native Americans.

• #11 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hereditary hemochromatosis is the most common autosomal recessive disorder in White populations, with a prevalence of 1 in 300 to 500 individuals. […] The prevalence of hemochromatosis is the same in Europe, Australia, and other Western countries, with excess in people of Celtic or Scandinavian origin. Hemochromatosis is less prevalent in patients of African descent. White individuals have a 6 times higher risk of developing the disease than Black individuals. […] In hemochromatosis, men are affected 2 to 3 times more often than women. The estimated ratio between men and women is 1.8:1 to 3:1. Women with hemochromatosis become symptomatic later in life than men due to the blood loss and consequent iron excretion associated with menstruation. The disease usually becomes apparent in men in the fifth decade; in women, it often presents in the sixth decade. […] Analyses of a p.C282Y homozygous genotypic subset have revealed the greatest morbidity is in those patients older than 60.

• #12 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  In populations of northern European ancestry, hereditary hemochromatosis is closely linked to mutations in HFE. In one study, more than 93% of Irish patients with hereditary hemochromatosis were homozygous for the HFE C282Y mutation, providing a reliable diagnostic marker of the disease in this population. […] Marked racial disparity in the distribution of the C282Y mutation has been noted. Prevalence of hemochromatosis is 6 times higher in White persons than in Black persons. In the Irish, the frequency of the C282Y mutation was 10%, whereas in Australian aboriginal, African, and Asian populations, the mutation has not been found. […] C282Y homozygotes account for 82-90% of clinical diagnoses of hereditary hemochromatosis among persons of northern European descent; in a report, 1 in 227 White individuals were homozygotes for the HFE C282Y mutation.

• #13 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  The frequency of the C282Y heterozygosity is much lower among Hispanic persons (0.27 per 1000 population), Asian Americans (0.001 per 1000 population), Pacific Islanders (0.12 per 1000 population), and Black persons (0.14 per 1000 population) than among persons of northern European descent. […] Men are affected with hemochromatosis nearly 2-3 times as often as women, with an estimated ratio of 1.8:1 to 3:1. […] Hemochromatosis usually becomes apparent after age 40 years in men (median age, 51 y) and after age 50 years in women (median age, 66 y). In women, onset of hereditary hemochromatosis begins later because menstruation causes physiologic blood loss, which increases iron removal.

• #14 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  In populations of northern European ancestry, hereditary hemochromatosis is closely linked to mutations in HFE. In one study, more than 93% of Irish patients with hereditary hemochromatosis were homozygous for the HFE C282Y mutation, providing a reliable diagnostic marker of the disease in this population. […] Marked racial disparity in the distribution of the C282Y mutation has been noted. Prevalence of hemochromatosis is 6 times higher in White persons than in Black persons. In the Irish, the frequency of the C282Y mutation was 10%, whereas in Australian aboriginal, African, and Asian populations, the mutation has not been found. […] C282Y homozygotes account for 82-90% of clinical diagnoses of hereditary hemochromatosis among persons of northern European descent; in a report, 1 in 227 White individuals were homozygotes for the HFE C282Y mutation.

• #15 Hemochromatosis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Hemochromatosis_epidemiology_and_demographics

  Hemochromatosis is one of the most common inheritable genetic defects. […] In 2016, the incidence of C282Y is estimated to be 5400 cases per 100,000. […] In 2016, the incidence of H63D is estimated to be 13500 cases per 100,000. […] In 2017, the prevalence of Hemochromatosis was estimated to be from 500 case in 100000 individuals. […] The carrier state is estimated to be approximately 10000 in 100000. […] Prevalence of hemochromatosis is 6 times higher in white persons than in black persons. […] C282Y homozygotes account for 82-90% of clinical diagnoses of hereditary hemochromatosis among persons of northern European descent. […] Irish have highest prevalence of hemochromatosis. […] In 2005, estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites than in Native Americans.

• #16 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Prevalence of hereditary hemochromatosis in the United States is 1 case in 200-500 individuals. Most are of northern European origin. Frequency of the C282Y mutation is 5.4% and that of the H63D mutation is 13.5%. Prevalence of C282Y homozygosity has been estimated to be 0.26%, the H63D homozygosity was estimated to be 1.89%, and compound heterozygosity was estimated to be 1.97%. The carrier state is estimated to be approximately 10%. […] The worldwide frequency of the C282Y is about 1.9% and that of the H63D mutation is about 8.1%. Hemochromatosis has the same prevalence in Europe, Australia, and other Western countries, with the highest prevalence being noted in people of Celtic origin. Hemochromatosis is less common among patients of African descent. […] Marked geographical disparity in the distribution of the C282Y mutation has been noted. Non-HFE- associated hereditary hemochromatosis was found in Mediterranean countries.

• #17 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Haemochromatosis is one of the most common heritable genetic conditions in people of Northern Europe, with a prevalence of 1:200. The disease has a variable penetration, and about one in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism. In the U.S., the frequency of the C282Y and H63D mutations is 5.4% and 13.5%, respectively. Whereas, the worldwide frequency of the C282Y and H63D mutations is about 1.9% and 8.1%, respectively, so mutation in H63D allele are more than C282Y allele. The prevalence of mutations in iron-metabolism genes varies in different populations. A study of 3,011 unrelated white Australians found that 14% were heterozygous carriers of an HFE mutation, 0.5% were homozygous for an HFE mutation, and only 0.25% of the study population had clinically relevant iron overload. Most patients who are homozygous for HFE mutations do not manifest clinically relevant haemochromatosis. Other populations have a lower prevalence of both the genetic mutation and the clinical disease. It is the most frequent genetic disease in the U.S. with a prevalence of 1:300 in the non-Hispanic white population. It is 2-3 times more common in males.

• #18 Epidemiology – GPnotebook

  https://gpnotebook.com/en-IE/pages/gastroenterology/hereditary-haemochromatosis-hh/epidemiology

  Hereditary haemochromatosis is a condition seen throughout the world (1). […] it is the most common single gene disorder in North European populations, especially Nordic or Celtic ancestry, in which it occurs with a prevalence of approximately 1 per 220-250 individuals (1,2) […] a systemic review has reported that 0.4% of people of northern European descent have the genetic mutation that increases the risk of developing haemochromatosis […] however the clinical penetrance of the mutation is much lower than the genetic prevalence. […] Around 80% of cases display homozygous C282Y mutation of the HFE gene on chromosome 6. […] homozygous C282Y mutation affects nearly 1 in 250 white people […] estimated prevalence among non white population is low 0.00004- 0.1% […] in population screening studies, 25-50% of the homozygotes are found to be asymptomatic. […] Compound heterozygosity for C282Y/H63D is present in 4-7% of patients while homozygous H63D is seen in around 1% (1). […] Around 5% are non HFE mutations (1).

• #19 Hemochromatosis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Hemochromatosis_epidemiology_and_demographics

  Non-Hispanic whites 44000 cases in 100000. […] Native Americans 11000 cases in 100000. […] Hispanics 270 cases in 100000. […] Blacks 140 cases in 100000. […] Pacific Islanders cases 120 in 100000. […] Asians less then 1 case in 100000. […] The European countries with the highest prevalence include Ireland, France, and Denmark.

• #20 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  The frequency of the C282Y heterozygosity is much lower among Hispanic persons (0.27 per 1000 population), Asian Americans (0.001 per 1000 population), Pacific Islanders (0.12 per 1000 population), and Black persons (0.14 per 1000 population) than among persons of northern European descent. […] Men are affected with hemochromatosis nearly 2-3 times as often as women, with an estimated ratio of 1.8:1 to 3:1. […] Hemochromatosis usually becomes apparent after age 40 years in men (median age, 51 y) and after age 50 years in women (median age, 66 y). In women, onset of hereditary hemochromatosis begins later because menstruation causes physiologic blood loss, which increases iron removal.

• #21 Hemochromatosis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Hemochromatosis_epidemiology_and_demographics

  Non-Hispanic whites 44000 cases in 100000. […] Native Americans 11000 cases in 100000. […] Hispanics 270 cases in 100000. […] Blacks 140 cases in 100000. […] Pacific Islanders cases 120 in 100000. […] Asians less then 1 case in 100000. […] The European countries with the highest prevalence include Ireland, France, and Denmark.

• #22 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  The frequency of the C282Y heterozygosity is much lower among Hispanic persons (0.27 per 1000 population), Asian Americans (0.001 per 1000 population), Pacific Islanders (0.12 per 1000 population), and Black persons (0.14 per 1000 population) than among persons of northern European descent. […] Men are affected with hemochromatosis nearly 2-3 times as often as women, with an estimated ratio of 1.8:1 to 3:1. […] Hemochromatosis usually becomes apparent after age 40 years in men (median age, 51 y) and after age 50 years in women (median age, 66 y). In women, onset of hereditary hemochromatosis begins later because menstruation causes physiologic blood loss, which increases iron removal.

• #23 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hereditary hemochromatosis is the most common autosomal recessive disorder in White populations, with a prevalence of 1 in 300 to 500 individuals. […] The prevalence of hemochromatosis is the same in Europe, Australia, and other Western countries, with excess in people of Celtic or Scandinavian origin. Hemochromatosis is less prevalent in patients of African descent. White individuals have a 6 times higher risk of developing the disease than Black individuals. […] In hemochromatosis, men are affected 2 to 3 times more often than women. The estimated ratio between men and women is 1.8:1 to 3:1. Women with hemochromatosis become symptomatic later in life than men due to the blood loss and consequent iron excretion associated with menstruation. The disease usually becomes apparent in men in the fifth decade; in women, it often presents in the sixth decade. […] Analyses of a p.C282Y homozygous genotypic subset have revealed the greatest morbidity is in those patients older than 60.

• #24 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  The frequency of the C282Y heterozygosity is much lower among Hispanic persons (0.27 per 1000 population), Asian Americans (0.001 per 1000 population), Pacific Islanders (0.12 per 1000 population), and Black persons (0.14 per 1000 population) than among persons of northern European descent. […] Men are affected with hemochromatosis nearly 2-3 times as often as women, with an estimated ratio of 1.8:1 to 3:1. […] Hemochromatosis usually becomes apparent after age 40 years in men (median age, 51 y) and after age 50 years in women (median age, 66 y). In women, onset of hereditary hemochromatosis begins later because menstruation causes physiologic blood loss, which increases iron removal.

• #25 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hereditary hemochromatosis is the most common autosomal recessive disorder in White populations, with a prevalence of 1 in 300 to 500 individuals. […] The prevalence of hemochromatosis is the same in Europe, Australia, and other Western countries, with excess in people of Celtic or Scandinavian origin. Hemochromatosis is less prevalent in patients of African descent. White individuals have a 6 times higher risk of developing the disease than Black individuals. […] In hemochromatosis, men are affected 2 to 3 times more often than women. The estimated ratio between men and women is 1.8:1 to 3:1. Women with hemochromatosis become symptomatic later in life than men due to the blood loss and consequent iron excretion associated with menstruation. The disease usually becomes apparent in men in the fifth decade; in women, it often presents in the sixth decade. […] Analyses of a p.C282Y homozygous genotypic subset have revealed the greatest morbidity is in those patients older than 60.

• #26 researchopenworld.com

  https://researchopenworld.com/discussing-why-hemochromatosis-is-ignored/

  Although the number of people with hemochromatosis is quite low, there could be cases out there that have yet to be diagnosed or that have been mistaken for other chronic diseases. […] The signs of hereditary hemochromatosis usually do not appear until about age between 40 and 60 years, when iron in the body has reached damaging levels. […] Because women lose iron to a greater extent than men because of menses, pregnancy, and lactation, they tend to become symptomatic slightly later in life than men, often after menopause. […] The screening process is the main thrust of this paper, since the disease is common and complications can be easily prevented with early diagnosis and treatment, the question of community screening has been raised and much debate has ensued. […] Here in the USA a number of medical doctors

• #27 Hemochromatosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/haemochromatosis?embed_domain=hackmd.io%25252F%252540yIPUAFeCSL2JsU8smR5nJQ%25252Fbnjhjgjghjghjgh&lang=us

  Hemochromatosis may be primary which is a genetic disorder or secondary which can result from a variety of diseases. […] Primary hemochromatosis is primarily (90%) due to an abnormal HFE gene, the protein product of which regulates iron absorption from the gastrointestinal tract. […] Approximately 2-5% of the population are heterozygous carriers (Caucasian population), resulting in a 0.2-0.5% prevalence of homozygous individuals. This makes hemochromatosis one of the most common genetic disorders in Caucasians of Northern European ancestry. […] Although the genetic defect is distributed equally among men and women, the iron loss as a result of menstruation is protective, resulting in a clinical male predilection (M:F ~ 2:1). […] In men, the diagnosis usually becomes evident in middle age (30-40 years of age) whereas, in women, clinical manifestation is delayed until the post-menopausal period. […] Secondary hemochromatosis is rare and is usually seen in association with diseases that chiefly cause hemosiderosis.

• #28 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hereditary hemochromatosis is the most common autosomal recessive disorder in White populations, with a prevalence of 1 in 300 to 500 individuals. […] The prevalence of hemochromatosis is the same in Europe, Australia, and other Western countries, with excess in people of Celtic or Scandinavian origin. Hemochromatosis is less prevalent in patients of African descent. White individuals have a 6 times higher risk of developing the disease than Black individuals. […] In hemochromatosis, men are affected 2 to 3 times more often than women. The estimated ratio between men and women is 1.8:1 to 3:1. Women with hemochromatosis become symptomatic later in life than men due to the blood loss and consequent iron excretion associated with menstruation. The disease usually becomes apparent in men in the fifth decade; in women, it often presents in the sixth decade. […] Analyses of a p.C282Y homozygous genotypic subset have revealed the greatest morbidity is in those patients older than 60.

• #29 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  The frequency of the C282Y heterozygosity is much lower among Hispanic persons (0.27 per 1000 population), Asian Americans (0.001 per 1000 population), Pacific Islanders (0.12 per 1000 population), and Black persons (0.14 per 1000 population) than among persons of northern European descent. […] Men are affected with hemochromatosis nearly 2-3 times as often as women, with an estimated ratio of 1.8:1 to 3:1. […] Hemochromatosis usually becomes apparent after age 40 years in men (median age, 51 y) and after age 50 years in women (median age, 66 y). In women, onset of hereditary hemochromatosis begins later because menstruation causes physiologic blood loss, which increases iron removal.

• #30 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Hereditary hemochromatosis is the most common inherited disorder among people of northern European ancestry. […] The United States, Europe, and Australia have a similar disease prevalence of one case per 200 to 400 people, with the highest prevalence in those of Irish and Scandinavian ancestry. […] Despite the high prevalence of the gene mutation, there is a low and variable clinical penetrance, with up to 25% of people with C282Y homozygosity being clinically asymptomatic. […] The clinical manifestations of iron overload typically develop in the 40s or 50s. […] The disease is equally prevalent in men and women. Women typically present later in life when they are postmenopausal, likely because of menstrual blood loss delaying the development of symptomatic iron overload. […] The incidence of hepatocellular carcinoma is 20 to 200 times higher in patients with hereditary hemochromatosis, especially those with higher than stage 3 fibrosis and cirrhosis.

• #31 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Hereditary hemochromatosis is the most common inherited disorder among people of northern European ancestry. […] The United States, Europe, and Australia have a similar disease prevalence of one case per 200 to 400 people, with the highest prevalence in those of Irish and Scandinavian ancestry. […] Despite the high prevalence of the gene mutation, there is a low and variable clinical penetrance, with up to 25% of people with C282Y homozygosity being clinically asymptomatic. […] The clinical manifestations of iron overload typically develop in the 40s or 50s. […] The disease is equally prevalent in men and women. Women typically present later in life when they are postmenopausal, likely because of menstrual blood loss delaying the development of symptomatic iron overload. […] The incidence of hepatocellular carcinoma is 20 to 200 times higher in patients with hereditary hemochromatosis, especially those with higher than stage 3 fibrosis and cirrhosis.

• #32 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  The Centers for Disease Control and Prevention (CDC) does not recommend universal screening for hemochromatosis but rather suggests evaluating iron overload in individuals with a family history and in individuals who are symptomatic. […] Overall, the clinical expressivity of C282Y homozygosity appears to be much lower than previously thought, and the cost effectiveness of screening has been challenged, because many people must be screened in order to prevent severe disease in only a few. […] Screening for hemochromatosis should be considered in the following individuals: All first-degree relatives of subjects known to have hemochromatosis: Human leukocyte antigen (HLA) typing is no longer necessary; family members identified as having C282Y homozygosity should be tested for transferrin saturation, serum ferritin, and liver enzymes; screening of young children of patients with hemochromatosis does not need to be performed if the spouse is tested and does not have the C282Y mutation.

• #33 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hereditary hemochromatosis is the most common autosomal recessive disorder in White populations, with a prevalence of 1 in 300 to 500 individuals. […] The prevalence of hemochromatosis is the same in Europe, Australia, and other Western countries, with excess in people of Celtic or Scandinavian origin. Hemochromatosis is less prevalent in patients of African descent. White individuals have a 6 times higher risk of developing the disease than Black individuals. […] In hemochromatosis, men are affected 2 to 3 times more often than women. The estimated ratio between men and women is 1.8:1 to 3:1. Women with hemochromatosis become symptomatic later in life than men due to the blood loss and consequent iron excretion associated with menstruation. The disease usually becomes apparent in men in the fifth decade; in women, it often presents in the sixth decade. […] Analyses of a p.C282Y homozygous genotypic subset have revealed the greatest morbidity is in those patients older than 60.

• #34 Clinical utility gene card for: Haemochromatosis [HFE] | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2009245

  In European populations, the incidence of C282Y homozygosity in individuals diagnosed with hereditary haemochromatosis ranges from 52% to 96%, with a stronger association seen in Northern European populations, in which the allele frequency is at its highest. […] The prevalence of the C282Y allele in Europe varies from 1.3% in Italy to 11.4% in Southern Ireland. H63D has an allele frequency ranging between 10% and 20% in Europe. […] Penetrance of risk genotypes is incomplete and is greater in males than in females. Absolute figures for penetrance are difficult to ascertain, owing to variations in individual study design relating to objective criteria for confirming a diagnosis of iron overload and potential ascertainment bias in individual study populations. However, with increasing age, the majority of C282Y homozygotes will manifest elevated iron indices, but only a small proportion of these (current best estimates indicate 12%) will develop significant clinical symptoms of iron overload. […] An estimated 50% of homozygous C282Y females will show evidence of iron accumulation, usually associated with slower progression to a disease state.

• #35 Clinical utility gene card for: Haemochromatosis [HFE] | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2009245

  In European populations, the incidence of C282Y homozygosity in individuals diagnosed with hereditary haemochromatosis ranges from 52% to 96%, with a stronger association seen in Northern European populations, in which the allele frequency is at its highest. […] The prevalence of the C282Y allele in Europe varies from 1.3% in Italy to 11.4% in Southern Ireland. H63D has an allele frequency ranging between 10% and 20% in Europe. […] Penetrance of risk genotypes is incomplete and is greater in males than in females. Absolute figures for penetrance are difficult to ascertain, owing to variations in individual study design relating to objective criteria for confirming a diagnosis of iron overload and potential ascertainment bias in individual study populations. However, with increasing age, the majority of C282Y homozygotes will manifest elevated iron indices, but only a small proportion of these (current best estimates indicate 12%) will develop significant clinical symptoms of iron overload. […] An estimated 50% of homozygous C282Y females will show evidence of iron accumulation, usually associated with slower progression to a disease state.

• #36 Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank | The BMJ

  https://www.bmj.com/content/364/bmj.k5222

  We estimated associations between HFE p.C282Y status and common conditions potentially linked to haemochromatosis in the large United Kingdom Biobank genotyped sample. […] Overall penetrance (ie, having at least one diagnosis of haemochromatosis; any liver disease, including liver cancer; diabetes; osteoarthritis; or rheumatoid arthritis, including prevalent and incident diagnoses at end of follow-up, mean age 63.8 years) was 38.3% in p.C282Y homozygous men (all ages) compared with 15.7% in men with no p.C282Y mutations. […] In women, the respective estimates were 27.2% versus 16.6%, excess morbidity 10.6%. […] These diagnostic rates are comparable to the eMERGE clinical biobank study across seven North American medical centres, which found that overall 24.4% of men and 14.0% of women p.C282Y homozygotes had a diagnosis of haemochromatosis.

• #37

  https://www.xiahepublishing.com/2310-8819/JCTH-2022-00373

  The regulation of iron homeostasis is a complicated process. Mutations of the HOE gene cause type 1 hemochromatosis. Mutations of several non-HFE genes result in four types of non-HFE hemochromatosis, namely HFE2 encoding HJV (type 2A), HAMP encoding hepcidin (type 2B), TFR2 encoding transferrin receptor-2 (type 3), and solute carrier family 40 member 1 (SLC40A1) encoding FPN. The allele frequencies of HJV (HFE2), TFR2, and HAMP mutations, range from 0.00007 to 0.0004. The SLC40A1 variant has been associated with persons of African descent and has a reported allele frequency of around 0.0004. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. […] The understanding of mutations underlying non-HFE hemochromatosis has significantly expanded with the wider availability and use of gene sequencing.

• #38 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Genetics studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60-70 generations ago. At that time, when dietary iron may have been scarcer than today, the presence of the mutant allele may have provided an evolutionary advantage by maintaining higher iron levels in the blood. […] The distribution of the C282Y variant was noted in various countries. Non-HFE associated hemochromatosis, as Haemochromatosis type 2, Haemochromatosis type 3, Haemochromatosis type 4 and Haemochromatosis type 5, were discovered in Mediterranean countries. On the other side, Northern European ancestry is closely linked to hereditary hemochromatosis disease (HFE). In one study, over 93% of Irish patients with HFE C282Y mutation were homozygotic. The G320V mutation in the HJV gene, which produces hemojuvelin protein, is widely distributed in central Europe and Greece.

• #39

  https://www.xiahepublishing.com/2310-8819/JCTH-2022-00373

  The regulation of iron homeostasis is a complicated process. Mutations of the HOE gene cause type 1 hemochromatosis. Mutations of several non-HFE genes result in four types of non-HFE hemochromatosis, namely HFE2 encoding HJV (type 2A), HAMP encoding hepcidin (type 2B), TFR2 encoding transferrin receptor-2 (type 3), and solute carrier family 40 member 1 (SLC40A1) encoding FPN. The allele frequencies of HJV (HFE2), TFR2, and HAMP mutations, range from 0.00007 to 0.0004. The SLC40A1 variant has been associated with persons of African descent and has a reported allele frequency of around 0.0004. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. […] The understanding of mutations underlying non-HFE hemochromatosis has significantly expanded with the wider availability and use of gene sequencing.

• #40

  https://xiahepublishing.com/2310-8819/JCTH-2022-00373

  The regulation of iron homeostasis is a complicated process. Mutations of the HOE gene cause type 1 hemochromatosis. Mutations of several non-HFE genes result in four types of non-HFE hemochromatosis, namely HFE2 encoding HJV (type 2A), HAMP encoding hepcidin (type 2B), TFR2 encoding transferrin receptor-2 (type 3), and solute carrier family 40 member 1 (SLC40A1) encoding FPN. The allele frequencies of HJV (HFE2), TFR2, and HAMP mutations, range from 0.00007 to 0.0004. The SLC40A1 variant has been associated with persons of African descent and has a reported allele frequency of around 0.0004. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. […] The 2019 guidelines of the American College of Gastroenterology (ACG) hemochromatosis recommend magnetic resonance imaging (MRI) in evaluating liver iron concentrations in this patient population, followed by liver biopsy if necessary. Knowledge of the severity of iron deposition within the liver can guide therapy. With regard to establishing the type of hemochromatosis, the 2010 European Association for the Study of the Liver (EASL) guidelines recommend testing patients with high clinical suspicion of hemochromatosis (biochemical evidence or family history) for HFE mutations (C282Y) before considering screening for non-HFE mutations. The ACG 2019 guidelines, on the other hand, recommend against further genetic screening in patients who test negative for type 1 hemochromatosis. The same guidelines note a moderate quality of evidence for genetic counseling and screening for first-degree relatives of patients diagnosed with hemochromatosis.

• #41

  https://www.xiahepublishing.com/2310-8819/JCTH-2022-00373

  The regulation of iron homeostasis is a complicated process. Mutations of the HOE gene cause type 1 hemochromatosis. Mutations of several non-HFE genes result in four types of non-HFE hemochromatosis, namely HFE2 encoding HJV (type 2A), HAMP encoding hepcidin (type 2B), TFR2 encoding transferrin receptor-2 (type 3), and solute carrier family 40 member 1 (SLC40A1) encoding FPN. The allele frequencies of HJV (HFE2), TFR2, and HAMP mutations, range from 0.00007 to 0.0004. The SLC40A1 variant has been associated with persons of African descent and has a reported allele frequency of around 0.0004. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. […] The understanding of mutations underlying non-HFE hemochromatosis has significantly expanded with the wider availability and use of gene sequencing.

• #42

  https://xiahepublishing.com/2310-8819/JCTH-2022-00373

  The regulation of iron homeostasis is a complicated process. Mutations of the HOE gene cause type 1 hemochromatosis. Mutations of several non-HFE genes result in four types of non-HFE hemochromatosis, namely HFE2 encoding HJV (type 2A), HAMP encoding hepcidin (type 2B), TFR2 encoding transferrin receptor-2 (type 3), and solute carrier family 40 member 1 (SLC40A1) encoding FPN. The allele frequencies of HJV (HFE2), TFR2, and HAMP mutations, range from 0.00007 to 0.0004. The SLC40A1 variant has been associated with persons of African descent and has a reported allele frequency of around 0.0004. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. […] The 2019 guidelines of the American College of Gastroenterology (ACG) hemochromatosis recommend magnetic resonance imaging (MRI) in evaluating liver iron concentrations in this patient population, followed by liver biopsy if necessary. Knowledge of the severity of iron deposition within the liver can guide therapy. With regard to establishing the type of hemochromatosis, the 2010 European Association for the Study of the Liver (EASL) guidelines recommend testing patients with high clinical suspicion of hemochromatosis (biochemical evidence or family history) for HFE mutations (C282Y) before considering screening for non-HFE mutations. The ACG 2019 guidelines, on the other hand, recommend against further genetic screening in patients who test negative for type 1 hemochromatosis. The same guidelines note a moderate quality of evidence for genetic counseling and screening for first-degree relatives of patients diagnosed with hemochromatosis.

• #43

  https://www.xiahepublishing.com/2310-8819/JCTH-2022-00373

  The regulation of iron homeostasis is a complicated process. Mutations of the HOE gene cause type 1 hemochromatosis. Mutations of several non-HFE genes result in four types of non-HFE hemochromatosis, namely HFE2 encoding HJV (type 2A), HAMP encoding hepcidin (type 2B), TFR2 encoding transferrin receptor-2 (type 3), and solute carrier family 40 member 1 (SLC40A1) encoding FPN. The allele frequencies of HJV (HFE2), TFR2, and HAMP mutations, range from 0.00007 to 0.0004. The SLC40A1 variant has been associated with persons of African descent and has a reported allele frequency of around 0.0004. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. […] The understanding of mutations underlying non-HFE hemochromatosis has significantly expanded with the wider availability and use of gene sequencing.

• #44 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Genetics studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60-70 generations ago. At that time, when dietary iron may have been scarcer than today, the presence of the mutant allele may have provided an evolutionary advantage by maintaining higher iron levels in the blood. […] The distribution of the C282Y variant was noted in various countries. Non-HFE associated hemochromatosis, as Haemochromatosis type 2, Haemochromatosis type 3, Haemochromatosis type 4 and Haemochromatosis type 5, were discovered in Mediterranean countries. On the other side, Northern European ancestry is closely linked to hereditary hemochromatosis disease (HFE). In one study, over 93% of Irish patients with HFE C282Y mutation were homozygotic. The G320V mutation in the HJV gene, which produces hemojuvelin protein, is widely distributed in central Europe and Greece.

• #45 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Genetics studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60-70 generations ago. At that time, when dietary iron may have been scarcer than today, the presence of the mutant allele may have provided an evolutionary advantage by maintaining higher iron levels in the blood. […] The distribution of the C282Y variant was noted in various countries. Non-HFE associated hemochromatosis, as Haemochromatosis type 2, Haemochromatosis type 3, Haemochromatosis type 4 and Haemochromatosis type 5, were discovered in Mediterranean countries. On the other side, Northern European ancestry is closely linked to hereditary hemochromatosis disease (HFE). In one study, over 93% of Irish patients with HFE C282Y mutation were homozygotic. The G320V mutation in the HJV gene, which produces hemojuvelin protein, is widely distributed in central Europe and Greece.

• #46 Public health surveillance for hereditary hemochromatosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9867751/

  The recent realization that hemochromatosis is a common condition has created opportunities to develop unified public health surveillance for this disorder and its complications and to design programs to prevent unnecessary illness and death resulting from this disorder. […] Public health surveillance for hemochromatosis can be used to measure the magnitude of the problem (for example, to establish the number of persons with evidence of early iron overload); identify research needs; reveal the natural history of the disease; detect changes in health care practices, such as use of screening tests; and evaluate interventions, such as phlebotomy. […] Existing surveillance has been limited to periodic measurement of morbidity and mortality done by using hospital discharge records, health examination surveys, vital statistics, and data from small research registries.

• #47 Public health surveillance for hereditary hemochromatosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9867751/

  The recent realization that hemochromatosis is a common condition has created opportunities to develop unified public health surveillance for this disorder and its complications and to design programs to prevent unnecessary illness and death resulting from this disorder. […] Public health surveillance for hemochromatosis can be used to measure the magnitude of the problem (for example, to establish the number of persons with evidence of early iron overload); identify research needs; reveal the natural history of the disease; detect changes in health care practices, such as use of screening tests; and evaluate interventions, such as phlebotomy. […] Existing surveillance has been limited to periodic measurement of morbidity and mortality done by using hospital discharge records, health examination surveys, vital statistics, and data from small research registries.

• #48 Public health surveillance for hereditary hemochromatosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9867751/

  The improvement of surveillance will entail the ongoing collection of information from population-based surveys, such as the Behavioral Risk Factor Surveillance System; the collection of data on provider practices (for example, through the National Ambulatory Medical Care Survey); and the establishment of population-based registries. […] Creating population-based registries requires consensus on case definitions; strategies to encourage case ascertainment and reporting; policies and procedures for protecting privacy and ensuring confidentiality; and partnerships among providers, researchers, and public health officials. […] Longitudinal data from population-based registries will provide insight into determinants of disease expression, such as pattern or degree of iron overload. […] This information is critical for developing evidence-based recommendations for population screening, monitoring changes in medical practices, and assessing the effect of preventive measures.

• #49 Public health surveillance for hereditary hemochromatosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9867751/

  The improvement of surveillance will entail the ongoing collection of information from population-based surveys, such as the Behavioral Risk Factor Surveillance System; the collection of data on provider practices (for example, through the National Ambulatory Medical Care Survey); and the establishment of population-based registries. […] Creating population-based registries requires consensus on case definitions; strategies to encourage case ascertainment and reporting; policies and procedures for protecting privacy and ensuring confidentiality; and partnerships among providers, researchers, and public health officials. […] Longitudinal data from population-based registries will provide insight into determinants of disease expression, such as pattern or degree of iron overload. […] This information is critical for developing evidence-based recommendations for population screening, monitoring changes in medical practices, and assessing the effect of preventive measures.

• #50 Public health surveillance for hereditary hemochromatosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9867751/

  The improvement of surveillance will entail the ongoing collection of information from population-based surveys, such as the Behavioral Risk Factor Surveillance System; the collection of data on provider practices (for example, through the National Ambulatory Medical Care Survey); and the establishment of population-based registries. […] Creating population-based registries requires consensus on case definitions; strategies to encourage case ascertainment and reporting; policies and procedures for protecting privacy and ensuring confidentiality; and partnerships among providers, researchers, and public health officials. […] Longitudinal data from population-based registries will provide insight into determinants of disease expression, such as pattern or degree of iron overload. […] This information is critical for developing evidence-based recommendations for population screening, monitoring changes in medical practices, and assessing the effect of preventive measures.

• #51 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  The Centers for Disease Control and Prevention (CDC) does not recommend universal screening for hemochromatosis but rather suggests evaluating iron overload in individuals with a family history and in individuals who are symptomatic. […] Overall, the clinical expressivity of C282Y homozygosity appears to be much lower than previously thought, and the cost effectiveness of screening has been challenged, because many people must be screened in order to prevent severe disease in only a few. […] Screening for hemochromatosis should be considered in the following individuals: All first-degree relatives of subjects known to have hemochromatosis: Human leukocyte antigen (HLA) typing is no longer necessary; family members identified as having C282Y homozygosity should be tested for transferrin saturation, serum ferritin, and liver enzymes; screening of young children of patients with hemochromatosis does not need to be performed if the spouse is tested and does not have the C282Y mutation.

• #52 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  The Centers for Disease Control and Prevention (CDC) does not recommend universal screening for hemochromatosis but rather suggests evaluating iron overload in individuals with a family history and in individuals who are symptomatic. […] Overall, the clinical expressivity of C282Y homozygosity appears to be much lower than previously thought, and the cost effectiveness of screening has been challenged, because many people must be screened in order to prevent severe disease in only a few. […] Screening for hemochromatosis should be considered in the following individuals: All first-degree relatives of subjects known to have hemochromatosis: Human leukocyte antigen (HLA) typing is no longer necessary; family members identified as having C282Y homozygosity should be tested for transferrin saturation, serum ferritin, and liver enzymes; screening of young children of patients with hemochromatosis does not need to be performed if the spouse is tested and does not have the C282Y mutation.

• #53 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  As a result of the high frequency of hereditary hemochromatosis associated mutations, the American Medical Association recommended the establishment of guidelines for population screening. […] Screening tests for the general population comprise measurement of serum transferrin saturation or serum iron concentration; when transferrin saturation is greater than 60% or greater than 50% in women who are premenopausal, or when serum iron concentration is greater than 150 mcg/dL, other measurements are recommended. […] Measurement of transferrin saturation after an overnight fast should be considered the initial screening of individuals with suspected iron overload and first-degree relatives of patients with hereditary hemochromatosis older than 20 years. […] Clinical practice guidelines on hemochromatosis were published August 1, 2022 by the European Association for the Study of the Liver (EASL) in the Journal of Hepatology.

• #54 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  As a result of the high frequency of hereditary hemochromatosis associated mutations, the American Medical Association recommended the establishment of guidelines for population screening. […] Screening tests for the general population comprise measurement of serum transferrin saturation or serum iron concentration; when transferrin saturation is greater than 60% or greater than 50% in women who are premenopausal, or when serum iron concentration is greater than 150 mcg/dL, other measurements are recommended. […] Measurement of transferrin saturation after an overnight fast should be considered the initial screening of individuals with suspected iron overload and first-degree relatives of patients with hereditary hemochromatosis older than 20 years. […] Clinical practice guidelines on hemochromatosis were published August 1, 2022 by the European Association for the Study of the Liver (EASL) in the Journal of Hepatology.

• #55 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  The Centers for Disease Control and Prevention (CDC) does not recommend universal screening for hemochromatosis but rather suggests evaluating iron overload in individuals with a family history and in individuals who are symptomatic. […] Overall, the clinical expressivity of C282Y homozygosity appears to be much lower than previously thought, and the cost effectiveness of screening has been challenged, because many people must be screened in order to prevent severe disease in only a few. […] Screening for hemochromatosis should be considered in the following individuals: All first-degree relatives of subjects known to have hemochromatosis: Human leukocyte antigen (HLA) typing is no longer necessary; family members identified as having C282Y homozygosity should be tested for transferrin saturation, serum ferritin, and liver enzymes; screening of young children of patients with hemochromatosis does not need to be performed if the spouse is tested and does not have the C282Y mutation.

• #56 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  The Centers for Disease Control and Prevention (CDC) does not recommend universal screening for hemochromatosis but rather suggests evaluating iron overload in individuals with a family history and in individuals who are symptomatic. […] Overall, the clinical expressivity of C282Y homozygosity appears to be much lower than previously thought, and the cost effectiveness of screening has been challenged, because many people must be screened in order to prevent severe disease in only a few. […] Screening for hemochromatosis should be considered in the following individuals: All first-degree relatives of subjects known to have hemochromatosis: Human leukocyte antigen (HLA) typing is no longer necessary; family members identified as having C282Y homozygosity should be tested for transferrin saturation, serum ferritin, and liver enzymes; screening of young children of patients with hemochromatosis does not need to be performed if the spouse is tested and does not have the C282Y mutation.

• #57 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  Patients who should receive genetic testing for hemochromatosis include individuals with elevated serum ferritin and transferrin saturation, clinical and biochemical symptoms of hemochromatosis, or idiopathic persistently elevated transferrin saturation. […] Adults with first-degree relatives diagnosed with hemochromatosis should receive genetic testing. […] Evaluation of serum iron results should be the primary assessment for hemochromatosis. […] Genotype should not be the sole guiding factor in the management of patients with p.C282Y/p.H63D compound heterozygosity or p.H63D homozygosity. […] Assessment for liver fibrosis should be non-invasively performed at the time of diagnosis for all patients with hemochromatosis. […] Public health surveillance for hereditary hemochromatosis. […] Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians.

• #58 Hemochromatosis Guidelines: Guidelines Summary, Hemochromatosis Clinical Practice Guidelines (EASL, 2022)

  https://emedicine.medscape.com/article/177216-guidelines

  As a result of the high frequency of hereditary hemochromatosis associated mutations, the American Medical Association recommended the establishment of guidelines for population screening. […] Screening tests for the general population comprise measurement of serum transferrin saturation or serum iron concentration; when transferrin saturation is greater than 60% or greater than 50% in women who are premenopausal, or when serum iron concentration is greater than 150 mcg/dL, other measurements are recommended. […] Measurement of transferrin saturation after an overnight fast should be considered the initial screening of individuals with suspected iron overload and first-degree relatives of patients with hereditary hemochromatosis older than 20 years. […] Clinical practice guidelines on hemochromatosis were published August 1, 2022 by the European Association for the Study of the Liver (EASL) in the Journal of Hepatology.

• #59 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Hepatocellular carcinoma accounts for nearly 45% of deaths in patients with hereditary hemochromatosis. […] Liver imaging, with or without alpha-fetoprotein measurements, should be performed every six months for life to screen for hepatocellular carcinoma and monitor for the progression of cirrhosis. […] There is a twofold increased risk of colorectal and breast cancers in people with hereditary hemochromatosis C282Y homozygosity.

• #60 Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

  https://www.oaepublish.com/articles/2394-5079.2019.35

  HCC accounts for 25%-45% of disease-related premature deaths in HH. […] In HH, the primary risk factor for the development of HCC is the presence of cirrhosis. […] Studies that have assessed the association of risk factors for development of HCC in HH are listed in Tables 1 and 2. […] Collectively, these data illustrate that the presence of cirrhosis is the primary risk factor for the development of HCC in patients with HH. […] Importantly, some of these other risks can be reduced by lifestyle modifications and/or therapy of other liver diseases, particularly chronic viral hepatitis.

• #61 Hereditary Hemochromatosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0201/p183.html

  Hereditary hemochromatosis is the most common genetic disease in whites. […] Universal screening for hereditary hemochromatosis is not recommended, but testing should be performed in first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results. […] Hereditary hemochromatosis is more common in white populations of northern European origin and is highest in Ireland; the prevalence ranges from one in 150 to 250 persons. […] Hepatocellular carcinoma accounts for approximately 30 percent of deaths in patients with hereditary hemochromatosis. […] Patients with hereditary hemochromatosis and cirrhosis should have screening ultrasonography every six to 12 months.

• #62 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Hereditary hemochromatosis is the most common inherited disorder among people of northern European ancestry. […] The United States, Europe, and Australia have a similar disease prevalence of one case per 200 to 400 people, with the highest prevalence in those of Irish and Scandinavian ancestry. […] Despite the high prevalence of the gene mutation, there is a low and variable clinical penetrance, with up to 25% of people with C282Y homozygosity being clinically asymptomatic. […] The clinical manifestations of iron overload typically develop in the 40s or 50s. […] The disease is equally prevalent in men and women. Women typically present later in life when they are postmenopausal, likely because of menstrual blood loss delaying the development of symptomatic iron overload. […] The incidence of hepatocellular carcinoma is 20 to 200 times higher in patients with hereditary hemochromatosis, especially those with higher than stage 3 fibrosis and cirrhosis.

• #63 Hemochromatosis

  https://mobile.fpnotebook.com/GI/HemeOnc/Hmchrmts.htm

  Family History of Hemochromatosis increases risk, with a 25% risk if a sibling has Hemochromatosis and a 5% risk if a parent has Hemochromatosis. […] Surveillance for Hepatocellular Carcinoma includes obtaining RUQ Ultrasound every 6-12 months if no liver lesion is found. […] Liver Lesion 1 cm requires RUQ Ultrasound every 3-6 months and a gastroenterology consult. […] Hereditary Hemochromatosis increases risk of Hepatocellular Carcinoma 20-200 fold.

• #64 Hereditary Hemochromatosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0201/p183.html

  Hereditary hemochromatosis is the most common genetic disease in whites. […] Universal screening for hereditary hemochromatosis is not recommended, but testing should be performed in first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results. […] Hereditary hemochromatosis is more common in white populations of northern European origin and is highest in Ireland; the prevalence ranges from one in 150 to 250 persons. […] Hepatocellular carcinoma accounts for approximately 30 percent of deaths in patients with hereditary hemochromatosis. […] Patients with hereditary hemochromatosis and cirrhosis should have screening ultrasonography every six to 12 months.

• #65 Hemochromatosis – Rheumatology Advisor

  https://www.rheumatologyadvisor.com/ddi/hemochromatosis/

  There are two main types of hemochromatosis primary (also known as hereditary or classical hemochromatosis) and secondary. The most common type is primary, which is an inherited variation of the disease. The hereditary hemochromatosis carrier is a mutation in the HFE gene, known to some as the hemochromatosis gene, that is typically passed down in an autosomal recessive fashion. Secondary hemochromatosis refers to any other condition that could lead to an iron overload, such as anemia, blood transfusions, iron supplementation, long-term kidney dialysis, or liver disease. Within hereditary hemochromatosis, there are four distinct types. Type 1. Affects about 1 million Americans and is one of the most common genetic disorders in the United States. It mostly affects people with a lineage from northern Europe, and White populations have a six times greater risk of developing the disease than Black populations. The other 3 types are based on mutations: Type 2. An autosomal recessive disorder, which is divided into 2 parts, with 2a caused by mutations of hemojuvelin gene and 2b is caused by mutations of the hepcidin gene. Type 3. Autosomal recessive, caused by mutations of transferrin receptor-2 gene. Type 4. Autosomal dominant, caused by mutations of the ferroportin gene. Types 2 to 4 are considered rare. Men are also two to three times more likely to be affected by hemochromatosis than women. Due to the hereditary prevalence of the condition, first-degree relatives of hemochromatosis patients should undergo screening and genetic testing as well. Hepatocellular carcinoma accounts for roughly 30% of mortality in hemochromatosis, so all patients should undergo surveillance with biannual checks of alpha-fetoprotein levels and ultrasound.

• #66 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Hepatocellular carcinoma accounts for nearly 45% of deaths in patients with hereditary hemochromatosis. […] Liver imaging, with or without alpha-fetoprotein measurements, should be performed every six months for life to screen for hepatocellular carcinoma and monitor for the progression of cirrhosis. […] There is a twofold increased risk of colorectal and breast cancers in people with hereditary hemochromatosis C282Y homozygosity.

• #67 The epidemiology and case identification of Genetic Haemochromatosis in the UK General Population | CPRD

  https://www.cprd.com/approved-studies/epidemiology-and-case-identification-genetic-haemochromatosis-uk-general

  Genetic Haemochromatosis is a common inherited condition which causes a build-up of iron in the body, known as iron overload. […] Unfortunately, while it is thought that approximately 1.2 million people in the UK are affected by the genetic defect for hereditary haemochromatosis, fewer than 20,000 are diagnosed with the disease, with the majority of individuals being symptomatic for up to ten years before diagnosis. […] The low rate of diagnosis of hemochromatosis in the early stages of the disease is partly because not all individuals will present with symptoms, symptoms of the disease are relatively non-specific and are common presentations in clinical practice, but there is also poor awareness of the condition among health care professionals. […] Earlier identification and treatment of GH can reduce the risk of these complications, but current evidence suggests that the majority of individuals with GH remain undiagnosed.

• #68 The epidemiology and case identification of Genetic Haemochromatosis in the UK General Population | CPRD

  https://www.cprd.com/approved-studies/epidemiology-and-case-identification-genetic-haemochromatosis-uk-general

  Genetic Haemochromatosis is a common inherited condition which causes a build-up of iron in the body, known as iron overload. […] Unfortunately, while it is thought that approximately 1.2 million people in the UK are affected by the genetic defect for hereditary haemochromatosis, fewer than 20,000 are diagnosed with the disease, with the majority of individuals being symptomatic for up to ten years before diagnosis. […] The low rate of diagnosis of hemochromatosis in the early stages of the disease is partly because not all individuals will present with symptoms, symptoms of the disease are relatively non-specific and are common presentations in clinical practice, but there is also poor awareness of the condition among health care professionals. […] Earlier identification and treatment of GH can reduce the risk of these complications, but current evidence suggests that the majority of individuals with GH remain undiagnosed.

• #69 The epidemiology and case identification of Genetic Haemochromatosis in the UK General Population | CPRD

  https://www.cprd.com/approved-studies/epidemiology-and-case-identification-genetic-haemochromatosis-uk-general

  Genetic Haemochromatosis is a common inherited condition which causes a build-up of iron in the body, known as iron overload. […] Unfortunately, while it is thought that approximately 1.2 million people in the UK are affected by the genetic defect for hereditary haemochromatosis, fewer than 20,000 are diagnosed with the disease, with the majority of individuals being symptomatic for up to ten years before diagnosis. […] The low rate of diagnosis of hemochromatosis in the early stages of the disease is partly because not all individuals will present with symptoms, symptoms of the disease are relatively non-specific and are common presentations in clinical practice, but there is also poor awareness of the condition among health care professionals. […] Earlier identification and treatment of GH can reduce the risk of these complications, but current evidence suggests that the majority of individuals with GH remain undiagnosed.

• #70 The epidemiology and case identification of Genetic Haemochromatosis in the UK General Population | CPRD

  https://www.cprd.com/approved-studies/epidemiology-and-case-identification-genetic-haemochromatosis-uk-general

  Aim: To improve the identification and understanding of genetic haemochromatosis in the UK General population. […] To improve understanding and provide contemporary evidence on the incidence of genetic haemochromatosis in primary care, adverse health outcomes associated with the condition, and improve case-identification of haemochromatosis in primary care.

• #71 Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review

  https://www.mdpi.com/2077-0383/13/13/3660

  The diagnostic approach to a patient with HC suspicion may be challenging. […] The only way to eliminate it is passive loss through menstrual blood, bleeding, exfoliation of epithelium, etc. […] Screening for HFE mutations is not recommended in the general population. […] However, genetic evaluation may be required in patients with chronic liver disease with unclear etiology and TSAT above 45%. […] Therefore, early identification of patients with clinical features suggestive of HC and their appropriate management remains fundamental to preventing multi-organ damage with further clinical complications and ensuring normal life expectancy. […] This goal could be achieved by targeted case detection, although previous population screening studies have revealed that HC penetrance is lower than expected. […] However, screening among at least Caucasian men of Northern European ancestry seems to be reasonable.

• #72 Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review

  https://www.mdpi.com/2077-0383/13/13/3660

  The diagnostic approach to a patient with HC suspicion may be challenging. […] The only way to eliminate it is passive loss through menstrual blood, bleeding, exfoliation of epithelium, etc. […] Screening for HFE mutations is not recommended in the general population. […] However, genetic evaluation may be required in patients with chronic liver disease with unclear etiology and TSAT above 45%. […] Therefore, early identification of patients with clinical features suggestive of HC and their appropriate management remains fundamental to preventing multi-organ damage with further clinical complications and ensuring normal life expectancy. […] This goal could be achieved by targeted case detection, although previous population screening studies have revealed that HC penetrance is lower than expected. […] However, screening among at least Caucasian men of Northern European ancestry seems to be reasonable.

• #73

  https://bpac.org.nz/bt/2015/april/haemochromatosis.aspx

  Patients with biochemical results suggestive of haemochromatosis which cannot be explained by other diagnoses should undergo genetic testing, particularly if they have a family history or symptoms and signs of haemochromatosis. […] Most cases of hereditary haemochromatosis (approximately 80%) are due to a patient inheriting a C282Y allele of the HFE gene from both parents (homozygous for the C282Y HFE allele). […] Genetic testing forms part of the diagnostic process and can provide some prognostic information, however, clinical management and treatment is the same for all individuals with hereditary haemochromatosis who develop iron overload, regardless of their underlying genotype. […] Patients with unexplained elevated ferritin or transferrin saturation, or clinical signs suggestive of haemochromatosis but without identified HFE risk alleles after referral to genetic testing services should be followed up, particularly if aged 20 years and under.

• #74 Hemochromatosis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Hemochromatosis_epidemiology_and_demographics

  Non-Hispanic whites 44000 cases in 100000. […] Native Americans 11000 cases in 100000. […] Hispanics 270 cases in 100000. […] Blacks 140 cases in 100000. […] Pacific Islanders cases 120 in 100000. […] Asians less then 1 case in 100000. […] The European countries with the highest prevalence include Ireland, France, and Denmark.

• #75 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  The frequency of the C282Y heterozygosity is much lower among Hispanic persons (0.27 per 1000 population), Asian Americans (0.001 per 1000 population), Pacific Islanders (0.12 per 1000 population), and Black persons (0.14 per 1000 population) than among persons of northern European descent. […] Men are affected with hemochromatosis nearly 2-3 times as often as women, with an estimated ratio of 1.8:1 to 3:1. […] Hemochromatosis usually becomes apparent after age 40 years in men (median age, 51 y) and after age 50 years in women (median age, 66 y). In women, onset of hereditary hemochromatosis begins later because menstruation causes physiologic blood loss, which increases iron removal.

• #76

  https://link.springer.com/article/10.1023/B:EJEP.0000017664.96394.b9

  Hereditary hemochromatosis is an iron overload disorder and is the most common recessive disease in Caucasians. About 80% of hemochromatosis patients are homozygous for the C282Y mutation in the HFE gene. Since iron accumulation can be prevented by phlebotomy, there is increasing interest in screening populations for hemochromatosis. Hemochromatosis is a disease that meets all the criteria for screening as set by the World Health Organization (WHO) or the US preventive services task force criteria for a screening program. However, there is no consensus on the value of a screening program for hemochromatosis. Moreover, there is no agreement on whether this screening should be based on the phenotype i.e. biochemical levels of serum iron parameters or on the genotype i.e. based on the presence of mutations in the HFE gene. Other important concerns are the lack of important data in evaluating screening as well as the psychosocial impact of a screening program.

• #77 Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank | The BMJ

  https://www.bmj.com/content/364/bmj.k5222

  Haemochromatosis is linked to more disease than previously thought […] In a large community sample, HFE p.C282Y homozygosity was associated with substantial prevalent and incident clinically diagnosed morbidity in both men and women. […] The p.C282Y variant is present in 10-15% of populations of northern European descent, with approximately 1/150 people being homozygotes. […] Studies of close relatives of patients with p.C282Y associated haemochromatosis suggested high penetrance to clinical disease: for example, Jacobs et al studied 735 first degree relatives of 224 Dutch p.C282Y homozygotes with clinically overt haemochromatosis and found 45.7% of these family members had a haemochromatosis related diagnosis compared with 19.4% in general population controls. […] However, several studies in general populations have suggested much lower penetrance to clinical disease.

• #78 Hereditary Hemochromatosis: Are We Ready for Population Screening? | CDC

  https://archive.cdc.gov/www_cdc_gov/genomics/events/hemochromatosis_2020.htm

  Hemochromatosis is a blood disorder in which the body builds up too much iron, damaging tissues and organs. In the United States, over 650,000 (1 in 300) non-Hispanic whites are homozygous for the C282Y mutation in the HFE gene, the most common genetic cause of hemochromatosis. […] His work showed that non-Hispanic white men who were homozygous for the C282Y mutation were more likely to be diagnosed with hemochromatosis, liver disease, diabetes mellitus, or arthritis and 1 in 5 had excess diagnoses of these conditions by an average age of 63 years. […] The iron overload seen in hemochromatosis can be treated, and even prevented, through phlebotomy. However, many with the condition do not know they have it and are not treated until after the iron overload has caused permanent damage. Is it time for population-based screening for the C282Y mutation?

• #79 Hereditary Hemochromatosis: Are We Ready for Population Screening? | CDC

  https://archive.cdc.gov/www_cdc_gov/genomics/events/hemochromatosis_2020.htm

  Hemochromatosis is a blood disorder in which the body builds up too much iron, damaging tissues and organs. In the United States, over 650,000 (1 in 300) non-Hispanic whites are homozygous for the C282Y mutation in the HFE gene, the most common genetic cause of hemochromatosis. […] His work showed that non-Hispanic white men who were homozygous for the C282Y mutation were more likely to be diagnosed with hemochromatosis, liver disease, diabetes mellitus, or arthritis and 1 in 5 had excess diagnoses of these conditions by an average age of 63 years. […] The iron overload seen in hemochromatosis can be treated, and even prevented, through phlebotomy. However, many with the condition do not know they have it and are not treated until after the iron overload has caused permanent damage. Is it time for population-based screening for the C282Y mutation?

• #80

  https://bpac.org.nz/bt/2015/april/haemochromatosis.aspx

  Following a diagnosis, the most important clinical steps are to investigate patients for the presence of haemochromatosis complications and initiate treatment. […] The key clinical intervention for treating haemochromatosis is venesection (phlebotomy) to reduce iron stores. […] Patients undergoing venesection often experience improvement in subjective symptoms of lethargy and abdominal pain, and changes in skin pigmentation. […] Studies suggest that patients with haemochromatosis who are adequately treated, and do not have liver cirrhosis or diabetes, have the same life expectancy as the general population. […] The development of liver disease is one of the most pressing concerns in the management of patients with haemochromatosis.

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