Materiały źródłowe

• #1 Hemochromatosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hemochromatosis/diagnosis-treatment/drc-20351448

  Hemochromatosis can be difficult to diagnose. Early symptoms such as stiff joints and fatigue may be due to conditions other than hemochromatosis. […] Many people with the disease don’t have any symptoms other than high levels of iron in their blood. Hemochromatosis may be identified because of irregular blood test results after testing is done for other reasons. It also may be revealed when screening family members of people diagnosed with the disease. […] The two key tests to detect iron overload are: […] Serum transferrin saturation. This test measures the amount of iron bound to the protein transferrin that carries iron in the blood. Transferrin saturation values greater than 45% are considered too high. […] Serum ferritin. This test measures the amount of iron stored in the liver. If the results of a serum transferrin saturation test are higher than usual, a healthcare professional may check serum ferritin levels.

• #2 Haemochromatosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/134

  Haemochromatosis is a genetic disorder causing a build-up of iron levels in the body over time. Elevated transferrin saturation is the phenotypic hallmark of the disorder, and diagnosis is confirmed by genetic testing. […] Key diagnostic factors include presence of risk factors, fatigue, weakness, lethargy, arthralgias, hepatomegaly, diabetes mellitus, impotence in males, amenorrhoea, loss of libido, and skin pigmentation. […] 1st investigations to order include serum transferrin saturation and serum ferritin. […] Investigations to consider include HFE mutation analysis, serum-based fibrosis tests/transient elastography, MRI liver, liver biopsy, LFTs, fasting blood sugar, echocardiogram, ECG, MRI heart and other organs, testosterone, FSH, and LH assays, and bone densitometry.

• #2 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  HEMOCHROMATOSIS DIAGNOSIS […] It is important to diagnose hemochromatosis early because early treatment can prevent complications. Diagnostic tests can help differentiate hemochromatosis from other conditions that cause similar symptoms, such as liver disease due to excess alcohol use. Tests can also determine the severity of hemochromatosis and its complications. […] […] Blood tests — Two blood tests are usually recommended to determine the amount of excess iron in the body. These tests may be done as part of an „iron studies panel.” […] […] Transferrin saturation — Transferrin is a protein that binds iron and transports it between the tissues. Some laboratories use a test called „total iron binding capacity” (TIBC), which essentially measures the same thing. The transferrin saturation (also called TSAT) measures the amount of iron bound to transferrin, which increases as the circulating iron increases. This test is the most sensitive for detecting early hemochromatosis. A TSAT higher than 45 percent should be investigated further. […]

• #3 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  Ferritin — Ferritin is a protein that reflects the body’s stores of iron. Blood ferritin levels increase when the body’s iron stores increase; however, levels of ferritin usually do not rise until iron stores are high. Therefore, the results of this test may be normal early in the course of hemochromatosis. Ferritin above 300 ng/mL in males or above 200 ng/mL in females supports a diagnosis of hemochromatosis. However, ferritin can also be increased by many disorders other than hemochromatosis. Only a small number of people with high ferritin actually have hemochromatosis. […] […] Genetic tests — Genetic testing can reveal the HFE C282Y variant associated with hemochromatosis. H63D is another variant seen in some people with hemochromatosis; however, its relevance to hemochromatosis is limited and controversial. There are also variants in other genes that can (very rarely) cause hemochromatosis, referred to as non-HFE hemochromatosis. […]

• #4 Hemochromatosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hemochromatosis/diagnosis-treatment/drc-20351448

  These blood tests for iron are best performed after fasting. Elevations in one or all of these tests can be found in other disorders. You may need to have the tests repeated for the most accurate results. […] A healthcare professional may suggest other tests to confirm the diagnosis and to look for other problems: […] Genetic testing is recommended for all parents, siblings and children of anyone diagnosed with hemochromatosis. If a gene change is found in only one parent, then children do not need to be tested.

• #5 Hemochromatosis Workup: Approach Considerations, Transferrin Saturation, Serum Ferritin Studies

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

  Serum abnormalities of iron metabolism can be seen in 50% of patients with alcoholic liver disease, NASH, or chronic viral hepatitis. […] Development of noninvasive measures of hepatic iron content has generated significant interest. […] Transferrin saturation corresponds to the ratio of serum iron and total iron-binding capacity (TIBC). […] If transferrin saturation is greater than 45%, the presence of the C282Y or H63D mutation may be evaluated to confirm the diagnosis of hemochromatosis. […] Hemochromatosis is suggested by a persistently elevated transferrin saturation in the absence of other causes of iron overload. […] Serum ferritin levels elevated higher than 200 mcg/L in premenopausal women and 300 mcg/L in men and postmenopausal women indicate primary iron overload due to hemochromatosis, especially when associated with high transferrin saturation and evidence of liver disease.

• #6 Diagnosis of Hemochromatosis – NIDDK

  https://www.niddk.nih.gov/health-information/liver-disease/hemochromatosis/diagnosis

  Doctors usually diagnose hemochromatosis based on blood test results. Doctors may first suspect hemochromatosis based on a medical and family history, a physical exam, and blood tests. […] Blood tests are critical for the diagnosis of hemochromatosis. In some cases, doctors may also order a liver biopsy. […] A high ratio of iron to transferrin in the blood may suggest a person has hemochromatosis. A high ferritin level is also typical in people who have hemochromatosis. Doctors may also use blood tests for ferritin levels to see if iron levels are improving with treatment. […] Doctors usually order blood tests to check for the gene mutations that cause hemochromatosis. Finding two copies of the HFE gene with the C282Y mutation confirms the diagnosis of primary hemochromatosis. […] In some cases, doctors will use a liver biopsy to confirm that iron overload is present and that no other liver diseases are present. The liver biopsy also shows whether iron overload has caused scarring or permanent damage to the liver.

• #7 Diagnosis of Hemochromatosis – NIDDK

  https://www.niddk.nih.gov/health-information/liver-disease/hemochromatosis/diagnosis

  Doctors usually diagnose hemochromatosis based on blood test results. Doctors may first suspect hemochromatosis based on a medical and family history, a physical exam, and blood tests. […] Blood tests are critical for the diagnosis of hemochromatosis. In some cases, doctors may also order a liver biopsy. […] A high ratio of iron to transferrin in the blood may suggest a person has hemochromatosis. A high ferritin level is also typical in people who have hemochromatosis. Doctors may also use blood tests for ferritin levels to see if iron levels are improving with treatment. […] Doctors usually order blood tests to check for the gene mutations that cause hemochromatosis. Finding two copies of the HFE gene with the C282Y mutation confirms the diagnosis of primary hemochromatosis. […] In some cases, doctors will use a liver biopsy to confirm that iron overload is present and that no other liver diseases are present. The liver biopsy also shows whether iron overload has caused scarring or permanent damage to the liver.

• #8 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  Ferritin — Ferritin is a protein that reflects the body’s stores of iron. Blood ferritin levels increase when the body’s iron stores increase; however, levels of ferritin usually do not rise until iron stores are high. Therefore, the results of this test may be normal early in the course of hemochromatosis. Ferritin above 300 ng/mL in males or above 200 ng/mL in females supports a diagnosis of hemochromatosis. However, ferritin can also be increased by many disorders other than hemochromatosis. Only a small number of people with high ferritin actually have hemochromatosis. […] […] Genetic tests — Genetic testing can reveal the HFE C282Y variant associated with hemochromatosis. H63D is another variant seen in some people with hemochromatosis; however, its relevance to hemochromatosis is limited and controversial. There are also variants in other genes that can (very rarely) cause hemochromatosis, referred to as non-HFE hemochromatosis. […]

• #9 Pathogenesis, Diagnostics, and Treatment of Hereditary Haemochromatosis: A 150 Year-Long Understanding of an Iron Overload Disorder – European Medical Journal

  https://www.emjreviews.com/hepatology/article/pathogenesis-diagnostics-and-treatment-of-hereditary-haemochromatosis-a-150-year-long-understanding-of-an-iron-overload-disorder/

  The aims in treating HH include diminishing of iron levels to the normal, preventing organ damage, treating possible complications such as liver disease, heart problems, or diabetes, and maintaining normal iron levels for the rest of life. […] Currently, the treatment of HH is based on phlebotomy therapy (venesection) and the elimination of iron by chelation therapy, depending on the aetiology. […] More recent findings suggest that the treatment with erythrocytapheresis is an alternative treatment. […] Hepcidin-targeted therapies in which novel therapeutics manipulate the mechanisms regulating hepcidin production could provide a more fundamental future approach in HH treatment. […] The significance of the second most frequent HFE mutation, H63D, is still unclear. […] In addition, the HFE S65C mutation may lead to mild hepatic iron overload, but does not encounter for clinical manifest haemochromatosis in most patients.

• #10 Sign up for our monthly newsletter

  https://www.haemochromatosis.org.uk/genetic-haemochromatosis-care-pathway

  Following a period of regular venesection, you will reach maintenance once your serum ferritin (SF) is below 100 g/l and transferrin saturation (TSAT) is below 50%. […] Genetic haemochromatosis is inherited, so its important that families consider genetic screening, based on their circumstances. […] If you have been diagnosed with genetic haemochromatosis c282y/c282y (known as c282y homozygote), doctors recommend that all your siblings, parents and adult children get tested for the condition. […] If you have been diagnosed with genetic haemochromatosis c282y/h63d (known as compound heterozygote), we also recommend that family members should be tested.

• #11 Hemochromatosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hemochromatosis/diagnosis-treatment/drc-20351448

  These blood tests for iron are best performed after fasting. Elevations in one or all of these tests can be found in other disorders. You may need to have the tests repeated for the most accurate results. […] A healthcare professional may suggest other tests to confirm the diagnosis and to look for other problems: […] Genetic testing is recommended for all parents, siblings and children of anyone diagnosed with hemochromatosis. If a gene change is found in only one parent, then children do not need to be tested.

• #12

  https://www.nhs.uk/conditions/haemochromatosis/diagnosis/

  Haemochromatosis can usually be diagnosed with blood tests. […] Several blood tests are needed to diagnose haemochromatosis. […] If your blood tests suggest haemochromatosis, you’ll have a test to see if your DNA carries the gene associated with the condition. […] These tests will help show if you have haemochromatosis, if you’re a carrier of a faulty gene linked to the condition, or if you might have another condition that causes high iron levels. […] If blood tests show that you have haemochromatosis, you may need to have some further tests to check if the condition has caused any organ damage, particularly damage to your liver.

• #13 Clinical manifestations and diagnosis of hereditary hemochromatosis – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemochromatosis

  Clinical manifestations and diagnosis of hereditary hemochromatosis […] Evaluation and diagnosis of HH requires integration of genetic information with other markers of tissue iron deposition. […] This topic reviews the pathophysiology, epidemiology, clinical manifestations, and diagnosis of HH. […] Diagnostic criteria […] Initial testing with iron studies […] Liver function tests […] HFE genetic testing […] Estimation of iron stores […] Diagnostic evaluation […] Indications for testing.

• #14 Hemochromatosis: Practice Essentials, Background, Pathophysiology

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

  Hemochromatosis is the abnormal accumulation of iron in parenchymal organs, leading to organ toxicity. The diagnosis of hemochromatosis is based on clinical features of the disease. Most patients are asymptomatic and are diagnosed when elevated serum iron levels are noted on a routine chemistry screening panel or when screening is performed because a relative is diagnosed with hemochromatosis. Laboratory studies used in evaluating suspected hemochromatosis include the following: Genetic testing: Examination of HFE mutations (C282Y, H63D) is pivotal for diagnosis of hemochromatosis. […] The use of liver biopsy in hereditary hemochromatosis can be restricted to those patients with a high probability of severe fibrosis or cirrhosis. The American Association for the Study of Liver Diseases (AASLD) guidelines include the following indications for liver biopsy: All homozygotes with clinical evidence of liver disease.

• #15 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  TESTS TO DIAGNOSE TISSUE IRON OVERLOAD […] Once a person has blood tests that show excess iron in their body, other tests are used to determine how much iron has been deposited in tissues such as the liver or heart. […] […] MRI methods — Magnetic resonance imaging (MRI) methods called R2, R2*, or T2* are most commonly used to determine levels of accumulation of iron in the liver and heart. […] […] Liver biopsy — A liver biopsy can be used to determine if the liver is affected by iron overload. This test is most useful if other causes of liver disease are being considered. In many straightforward cases, a liver biopsy is not necessary.

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

  https://radiopaedia.org/articles/haemochromatosis?lang=us

  Hemochromatosis is an iron overload disorder characterized by a progressive increase in total body iron stores and deposition of iron in some non-reticuloendothelial system (RES) body organs which results in some instances of organ dysfunction. […] 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. […] MRI is not only the most sensitive imaging modality for the diagnosis of hemochromatosis but is also able to estimate iron concentration within the liver, thus forestalling the need for repeated biopsies. […] In primary hemochromatosis, spleen and bone marrow signal is typically normal and low pancreatic signal is usually only seen if there is cirrhosis. […] Quantitative MR techniques for measuring iron deposition have been developed, consisting of multiple gradient-echo sequences with progressively increasing TEs. The degree to which signal drops can then be plotted and an estimate of iron concentration generated.

• #17 Hemochromatosis Workup: Approach Considerations, Transferrin Saturation, Serum Ferritin Studies

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

  Genetic tests for the C282Y and H63D mutations are widely available. […] Genetic testing for the HFE mutation is indicated in all first-degree relatives of patients with hemochromatosis and also in patients with evidence of iron overload. […] Currently, the diagnosis can be confidently based on genetic testing for the C282Y mutation; thus, liver biopsy is no longer essential for diagnosis in many cases. […] According to guidelines that were developed for the diagnosis and management of hereditary hemochromatosis, a liver biopsy is indicated in the following cases: (1) elevated liver enzymes in combination with hereditary hemochromatosis, and (2) serum ferritin levels greater than 1000 mcg/L. […] Liver biopsy should also be considered in compound or C282Y heterozygotes with elevated TS, particularly those who have had abnormal liver enzyme levels or clinical evidence of liver disease.

• #18 Hemochromatosis | Cleveland Clinic

  https://my.clevelandclinic.org/departments/digestive/medical-professionals/hepatology/hemochromatosis

  The diagnostic approach to HH may be targeted at distinct populations. […] Because it is agreed that clinical HH is the result of iron overload, the diagnosis is based on the documentation of increased iron storesnamely, increased hepatic iron concentrations associated with elevated serum ferritin levels. […] Now, with the availability of mutational analysis, HH may be further defined genotypically in a first-degree relative by the finding of C282Y homozygosity or C282Y-H63D compound heterozygosity. […] The initial step in the diagnostic approach to HH is the fasting transferrin iron saturation (TS). […] The second stage in the algorithm is genetic mutation analysis for the C282Y and H63D mutations of the HFE gene. […] The third step of the algorithm advances evaluation through therapeutic phlebotomy. […] It is therefore important to emphasize that the value of liver biopsy is not limited to determination of the HIC.

• #19 Recognition and Management of Hereditary Hemochromatosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0301/p853.html

  Hereditary hemochromatosis is the most common inherited single-gene disorder in people of northern European descent. […] The diagnosis is based on a combination of clinical, laboratory and pathologic findings, including elevated serum transferrin saturation. […] The diagnosis of hereditary hemochromatosis is based on a combination of clinical, laboratory and pathologic criteria, including an elevated serum transferrin saturation and an elevated serum ferritin concentration. […] An elevated serum transferrin saturation is the earliest phenotypic abnormality in hereditary hemochromatosis. […] Although the serum transferrin saturation is the best initial screening value, results may be normal early in the course of hereditary hemochromatosis. […] The serum ferritin concentration is a sensitive measure of iron overload, but it is also an acute-phase reactant and is therefore elevated in a variety of infectious and inflammatory conditions in the absence of iron overload.

• #20 Testing for HFE-related haemochromatosis – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/testing-for-hfe-related-haemochromatosis.html

  HFE-haemochromatosis is a genetic disorder resulting from mutations of the HFE gene. It primarily affects people of Northern European descent. An elevated serum ferritin concentration greater than 300 microgram/L and a transferrin saturation of greater than 45% will identify almost all patients with HFE-haemochromatosis. HFE genotyping confirms the diagnosis. […] The first approach to diagnosing HFE-haemochromatosis is the assessment of indirect markers of iron stores. Fasting transferrin saturation is considered to be the most sensitive screening test for HFE-haemochromatosis. […] An elevated fasting transferrin saturation greater than 50% in women and 60% in men of Northern European descent has a positive predictive value of 86% for the diagnosis of HFE-haemochromatosis. […] The combination of an elevated fasting transferrin saturation (greater than 45%) and an elevated serum ferritin has a negative predictive value of 97%. This exceeds the accuracy of either test used alone.

• #21 Haemochromatosis – Haemochromatosis Australia

  https://haemochromatosis.org.au/haemochromatosis/

  Hereditary haemochromatosis is diagnosed by simple blood tests. Your doctor may order the tests if your symptoms indicate haemochromatosis is possible or if you become aware a close relative has been diagnosed with the condition. […] These blood tests look for two indicators that signal someone may have haemochromatosis. They measure Transferrin Saturation and Serum Ferritin. They are usually a fasting blood test. […] If the results of these tests are above the reference range, they are repeated. If the second test again exceeds the range, a genetic blood test is necessary to confirm haemochromatosis. […] The gene associated with haemochromatosis is known as HFE. […] Haemochromatosis occurs when the genetic test shows they are homozygous, that is they have two faulty copies of the HFE gene. […] There is strong medical evidence of a potential for significant organ damage when iron stores cause serum ferritin levels above 1,000 g/L. However some people seem to experience symptoms with levels between 300 and 1,000 g/L. Higher levels are more likely to be associated with more severe symptoms.

• #22 Haemochromatosis – Haemochromatosis Australia

  https://haemochromatosis.org.au/haemochromatosis/

  Hereditary haemochromatosis is diagnosed by simple blood tests. Your doctor may order the tests if your symptoms indicate haemochromatosis is possible or if you become aware a close relative has been diagnosed with the condition. […] These blood tests look for two indicators that signal someone may have haemochromatosis. They measure Transferrin Saturation and Serum Ferritin. They are usually a fasting blood test. […] If the results of these tests are above the reference range, they are repeated. If the second test again exceeds the range, a genetic blood test is necessary to confirm haemochromatosis. […] The gene associated with haemochromatosis is known as HFE. […] Haemochromatosis occurs when the genetic test shows they are homozygous, that is they have two faulty copies of the HFE gene. […] There is strong medical evidence of a potential for significant organ damage when iron stores cause serum ferritin levels above 1,000 g/L. However some people seem to experience symptoms with levels between 300 and 1,000 g/L. Higher levels are more likely to be associated with more severe symptoms.

• #23 Haemochromatosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/134

  Haemochromatosis is a genetic disorder causing a build-up of iron levels in the body over time. Elevated transferrin saturation is the phenotypic hallmark of the disorder, and diagnosis is confirmed by genetic testing. […] Key diagnostic factors include presence of risk factors, fatigue, weakness, lethargy, arthralgias, hepatomegaly, diabetes mellitus, impotence in males, amenorrhoea, loss of libido, and skin pigmentation. […] 1st investigations to order include serum transferrin saturation and serum ferritin. […] Investigations to consider include HFE mutation analysis, serum-based fibrosis tests/transient elastography, MRI liver, liver biopsy, LFTs, fasting blood sugar, echocardiogram, ECG, MRI heart and other organs, testosterone, FSH, and LH assays, and bone densitometry.

• #24 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  TESTS TO DIAGNOSE TISSUE IRON OVERLOAD […] Once a person has blood tests that show excess iron in their body, other tests are used to determine how much iron has been deposited in tissues such as the liver or heart. […] […] MRI methods — Magnetic resonance imaging (MRI) methods called R2, R2*, or T2* are most commonly used to determine levels of accumulation of iron in the liver and heart. […] […] Liver biopsy — A liver biopsy can be used to determine if the liver is affected by iron overload. This test is most useful if other causes of liver disease are being considered. In many straightforward cases, a liver biopsy is not necessary.

• #25 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  Investigations and diagnosis of hereditary haemochromatosis involves assessment of iron overload, genetics and organ damage. These tests need careful interpretation. […] HFE testing for the C282Y and H63D polymorphism should be carried out in all patients with otherwise unexplained increased serum ferritin and increased transferrin saturation. […] C282Y homozygosity is required for the diagnosis of HFE-HC, when iron stores are increased. […] Diagnosis of HFE haemochromatosis should not be based on C282Y homozygosity alone but requires evidence of increased iron stores. […] In C282Y homozygote patients with increased iron stores, liver biopsy is no longer necessary to diagnose haemochromatosis. […] It is now rarely required because genetic testing for HFE mutations is very reliable in the diagnosis of haemochromatosis in Caucasians and the majority of patients with haemochromatosis are now diagnosed at an early stage, well before permanent tissue damage occurs.

• #26 Testing for HFE-related haemochromatosis – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/testing-for-hfe-related-haemochromatosis.html

  HFE-haemochromatosis is a genetic disorder resulting from mutations of the HFE gene. It primarily affects people of Northern European descent. An elevated serum ferritin concentration greater than 300 microgram/L and a transferrin saturation of greater than 45% will identify almost all patients with HFE-haemochromatosis. HFE genotyping confirms the diagnosis. […] The first approach to diagnosing HFE-haemochromatosis is the assessment of indirect markers of iron stores. Fasting transferrin saturation is considered to be the most sensitive screening test for HFE-haemochromatosis. […] An elevated fasting transferrin saturation greater than 50% in women and 60% in men of Northern European descent has a positive predictive value of 86% for the diagnosis of HFE-haemochromatosis. […] The combination of an elevated fasting transferrin saturation (greater than 45%) and an elevated serum ferritin has a negative predictive value of 97%. This exceeds the accuracy of either test used alone.

• #27

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

  Hereditary haemochromatosis is the most common genetic disease in European populations. Patients who have biochemical evidence of abnormal iron metabolism, measured by ferritin levels and transferrin saturation, require genetic testing after excluding non-specific causes of ferritin elevation. Haemochromatosis is usually a hereditary condition, characterised by increased iron absorption leading to iron deposition in tissues and ultimately organ damage. In 1996 it was discovered that approximately 80% 85% of cases of hereditary haemochromatosis are caused by common variants of the HFE gene. 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. Standard genetic testing for haemochromatosis assesses whether a patient has common risk alleles and how many copies they have. A diagnosis of HFE hereditary haemochromatosis can be made on the basis of biochemical signs of iron overload (increased ferritin and/or transferrin saturation) and the presence of risk alleles. 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.

• #28 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  Investigations and diagnosis of hereditary haemochromatosis involves assessment of iron overload, genetics and organ damage. These tests need careful interpretation. […] HFE testing for the C282Y and H63D polymorphism should be carried out in all patients with otherwise unexplained increased serum ferritin and increased transferrin saturation. […] C282Y homozygosity is required for the diagnosis of HFE-HC, when iron stores are increased. […] Diagnosis of HFE haemochromatosis should not be based on C282Y homozygosity alone but requires evidence of increased iron stores. […] In C282Y homozygote patients with increased iron stores, liver biopsy is no longer necessary to diagnose haemochromatosis. […] It is now rarely required because genetic testing for HFE mutations is very reliable in the diagnosis of haemochromatosis in Caucasians and the majority of patients with haemochromatosis are now diagnosed at an early stage, well before permanent tissue damage occurs.

• #29 Symptoms and Diagnosis – Canadian Hemochromatosis Society

  https://www.toomuchiron.ca/hemochromatosis/symptoms-diagnosis/

  A positive HFE genetic test will implicate other family members who should also be tested. […] If the genetic test is negative because mutations (C282Y and H63D) were not detected in the HFE gene, then there may be another reason for iron overload, such as another disease, or another form of hemochromatosis caused by a different gene. Further medical investigation will be required. […] In addition to the biochemical blood screening tests (ferritin and transferrin saturation) and the genetic HFE test, there are other tests that can be ordered to help assess risk of, and monitor, injury to particular organs. […] Receiving your results and understanding what to do next can be a daunting prospect. The Canadian Hemochromatosis Society is here to help you understand your results, access treatment and provide ongoing support for you and your family.

• #30 Diagnosis and management of hereditary haemochromatosis | British Journal of General Practice

  https://bjgp.org/content/63/611/331

  If hereditary haemochromatosis is suspected, serum ferritin and transferrin saturation levels should be requested. Ferritin levels are raised and transferrin saturation 45% in presence of the disease. […] The next step is to determine the HFE genotype in those patients with a suggestive clinical presentation and blood parameters, although in practice referral to a specialist, usually a gastroenterologist is indicated. […] All patients with C282Y homozygosity, even if asymptomatic, should be treated and have regular follow up by a gastroenterologist, as it is currently not possible to predict that patients will go on to express the full manifestations of the disease. […] Evidence shows that initiating phlebotomy prior to the establishment of liver cirrhosis significantly reduces morbidity and mortality and patients without cirrhosis can expect to have a normal life expectancy. […] Siblings of patients with HFE-haemochromatosis should be screened with serum ferritin and transferrin saturation and ideally these individuals should undergo HFE genotyping after appropriate counselling.

• #31 Diagnosis and management of hereditary haemochromatosis | British Journal of General Practice

  https://bjgp.org/content/63/611/331

  If hereditary haemochromatosis is suspected, serum ferritin and transferrin saturation levels should be requested. Ferritin levels are raised and transferrin saturation 45% in presence of the disease. […] The next step is to determine the HFE genotype in those patients with a suggestive clinical presentation and blood parameters, although in practice referral to a specialist, usually a gastroenterologist is indicated. […] All patients with C282Y homozygosity, even if asymptomatic, should be treated and have regular follow up by a gastroenterologist, as it is currently not possible to predict that patients will go on to express the full manifestations of the disease. […] Evidence shows that initiating phlebotomy prior to the establishment of liver cirrhosis significantly reduces morbidity and mortality and patients without cirrhosis can expect to have a normal life expectancy. […] Siblings of patients with HFE-haemochromatosis should be screened with serum ferritin and transferrin saturation and ideally these individuals should undergo HFE genotyping after appropriate counselling.

• #32 Haemochromatosis – Gknowmix

  https://www.gknowmix.com/genetic-tests/iron-disorders-genescreen-info/haemochromatosis

  Haemochromatosis has been classified as the most common genetic disorder worldwide. […] Therefore, our pathology supported Haemochromatosis Test does not only focus on the identification or exclusion of genetic risk factors, but also the documentation of clinical conditions, abnormal biochemistry and environmental factors that may influence disease development. […] The clinical presentation of haemochromatosis has changed over recent years from diagnosing patients with advanced disease (e.g. liver cirrhosis, diabetes) to early detection of patients presenting with abnormal liver function tests, elevated ferritin and/or increased transferrin saturation levels. […] Determination of transferrin saturation is recommended as a first line screening method for haemochromatosis and can detect cases of iron overload before organ dysfunction has occurred.

• #33 Diagnosis and management of hereditary haemochromatosis | British Journal of General Practice

  https://bjgp.org/content/63/611/331

  Hereditary haemochromatosis is an autosomally recessive inherited genetic disorder associated with a defect in the iron regulating hormone hepcidin, causing increased intestinal absorption of iron and subsequent deposition in the liver, pancreas, heart, joints, skin, and gonads. […] A GP list of 2000 patients will have approximately four patients with hereditary haemochromatosis. Despite this, many GPs have never seen a case, although they are often best placed to make a diagnosis. […] GPs should have a high index of suspicion and consider testing for hereditary haemochromatosis in patients presenting with these persistent, vague symptoms. Other presentations include arthropathy, chondrocalcinosis, heart failure, erectile dysfunction, and porphyria cutanea tarda. […] Abnormal liver function tests should result in testing for hereditary haemochromatosis and is the most common route of diagnosis in primary care.

• #34 Symptoms and Diagnosis – Canadian Hemochromatosis Society

  https://www.toomuchiron.ca/hemochromatosis/symptoms-diagnosis/

  In spite of being the most common genetic disorder among persons of Northern European descent, hemochromatosis remains relatively unknown. […] Diagnosing the disorder before symptoms occur, while still in the early stages before irreversible damage is done, is extremely important. Many complications can be treated or prevented, but early diagnosis and therapy is the key. […] Currently, tests for hemochromatosis are not part of a general medical checkup. They must be specifically ordered on a blood lab requisition form. […] Serum ferritin and transferrin saturation measurements reflect how much iron is in the body and how much is being transported and stored. […] If both serum ferritin and transferrin saturation come back abnormally high, or even high normal, these screening blood tests may be repeated for accuracy. If the results continue to be elevated, then further medical work-up is required. Additional diagnostic testing can be done to confirm the presence of hemochromatosis. This includes genetic testing for the HFE gene.

• #35 Hereditary haemochromatosis – Wikipedia

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

  Liver biopsies involve taking a sample of tissue from the liver, using a thin needle. The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, is measured microscopically. […] MRI-based testing is a noninvasive and accurate alternative to measure liver iron concentrations. […] Standard diagnostic measures for haemochromatosis, transferrin saturation and ferritin tests, are not a part of routine medical testing. Screening for haemochromatosis is recommended if the patient has a parent, child, or sibling with the disease. […] Recently, patients are suggested to be screened for iron overload using serum ferritin as a marker. If serum ferritin exceeds 1000 ng/mL, iron overload is very likely the cause.

• #36 Genetic Testing for Hereditary Hemochromatosis

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/genetic-testing-for-hereditary-hemochromatosis/

  The ACG recommends that patients with abnormal iron studies should be evaluated as patients with hemochromatosis, even in the absence of symptoms. […] The ACG also recommends that individuals with the H63D or S65C mutation in the absence of C282Y mutation should be counseled that they are not at increased risk of iron overload. […] The USPSTF recommends against genetic screening for HH in the general, asymptomatic population, due to the low penetrance of the disease among those with causative mutations. […] The EASL published clinical practice guidelines for HFE hemochromatosis. […] Genotyping for p.C282Y in HFE should be carried out in individuals of European origin with biochemical evidence of iron overload. […] Testing adult siblings of p.C282Y homozygotes is recommended owing to the increased risk of p.C282Y homozygosity and related increased morbidity.

• #37 About Hereditary Hemochromatosis | Hereditary Hemochromatosis | CDC

  https://www.cdc.gov/hereditary-hemochromatosis/about/index.html

  Early diagnosis and treatment are critical to prevent complications from the disease. […] A blood test can be used to screen people who may have hemochromatosis by measuring how much iron is in their blood. Affected people with or without a known family history of hemochromatosis can be diagnosed through blood tests for excess iron in the body (called iron overload) followed by genetic testing. The earlier hemochromatosis is diagnosed, the less likely you are to develop serious complicationsmany of which can cause permanent problems.

• #38 P3 Genetic haemochromatosis: diagnosis and treatment experience | Gut

  https://gut.bmj.com/content/73/Suppl_3/A12.2

  Genetic haemochromatosis (GH) is the most common genetic disorder in Caucasians. Data from the UK Biobank indicates that 380, 000 individuals in the UK have GH. GH causes the body to absorb excess iron which can lead to systemic iron overload within internal organs such as the liver, pancreas, heart, and joints; eventually causing inflammation and tissue damage. […] Early symptoms are non-specific such as fatigue, abdominal and joint pain which can result in a delay in diagnosis and treatment increasing the risk of complications. […] Many patients interviewed talked about experiencing a delay; in some cases of many years, from first presentation of symptoms to their General Practitioner to final diagnosis. […] Many of the patients frequently felt that General Practitioners lacked sufficient knowledge about GH and could not provide detailed information about the disease.

• #39 P3 Genetic haemochromatosis: diagnosis and treatment experience | Gut

  https://gut.bmj.com/content/73/Suppl_3/A12.2

  Genetic haemochromatosis (GH) is the most common genetic disorder in Caucasians. Data from the UK Biobank indicates that 380, 000 individuals in the UK have GH. GH causes the body to absorb excess iron which can lead to systemic iron overload within internal organs such as the liver, pancreas, heart, and joints; eventually causing inflammation and tissue damage. […] Early symptoms are non-specific such as fatigue, abdominal and joint pain which can result in a delay in diagnosis and treatment increasing the risk of complications. […] Many patients interviewed talked about experiencing a delay; in some cases of many years, from first presentation of symptoms to their General Practitioner to final diagnosis. […] Many of the patients frequently felt that General Practitioners lacked sufficient knowledge about GH and could not provide detailed information about the disease.

• #40 P3 Genetic haemochromatosis: diagnosis and treatment experience | Gut

  https://gut.bmj.com/content/73/Suppl_3/A12.2

  This study identified that patients perceive significant gaps in General Practitioners understanding of GH. To enhance patient experience it is crucial for healthcare professionals to listen to and address patient concerns promptly throughout their treatment. These findings suggest that improved education for General Practitioners and other healthcare professionals involved in venesection could benefit patient care and improve the overall patient journey for those with haemochromatosis.

• #41 Hereditary haemochromatosis Diagnosis and management

  https://www.racgp.org.au/afp/2010/december/hereditary-haemochromatosis

  Hereditary haemochromatosis is a common inherited disorder in which excessive iron is absorbed and which, over time, may cause organ damage. […] This article discusses the presentation, testing, treatment and management of hereditary haemochromatosis. […] Most importantly, early diagnosis and treatment of hereditary haemochromatosis prevents complications and results in a normal life expectancy. […] Venesection is a simple and effective way to both prevent and manage the potential sequelae of iron overload, which include severe fatigue, arthritis, impotence, raised alanine aminotransferase/aspartate aminotransferase, fibrosis or cirrhosis, diabetes, and cardiomyopathy.

• #42 Haemochromatosis – British Liver Trust

  https://britishlivertrust.org.uk/information-and-support/liver-conditions/haemochromatosis/

  Diagnostic technology has been developed specifically for iron-overloading disease. […] Treatment of haemochromatosis is simply aimed at removing iron from your body. […] During phlebotomy a unit of blood, usually 450 millitres (ml), is removed. […] After your course of treatment you will need to have further phlebotomies two to four times a year for the rest of your life. […] If you have a family history of haemochromatosis, you should see a medical professional as soon as you can. […] Genetic counselling can help you to better understand the likely occurrence of haemochromatosis in your family or explain the implications of any diagnosis.

• #43 Sign up for our monthly newsletter

  https://www.haemochromatosis.org.uk/genetic-haemochromatosis-care-pathway

  Following a period of regular venesection, you will reach maintenance once your serum ferritin (SF) is below 100 g/l and transferrin saturation (TSAT) is below 50%. […] Genetic haemochromatosis is inherited, so its important that families consider genetic screening, based on their circumstances. […] If you have been diagnosed with genetic haemochromatosis c282y/c282y (known as c282y homozygote), doctors recommend that all your siblings, parents and adult children get tested for the condition. […] If you have been diagnosed with genetic haemochromatosis c282y/h63d (known as compound heterozygote), we also recommend that family members should be tested.

• #44 Sign up for our monthly newsletter

  https://www.haemochromatosis.org.uk/genetic-haemochromatosis-care-pathway

  Following a period of regular venesection, you will reach maintenance once your serum ferritin (SF) is below 100 g/l and transferrin saturation (TSAT) is below 50%. […] Genetic haemochromatosis is inherited, so its important that families consider genetic screening, based on their circumstances. […] If you have been diagnosed with genetic haemochromatosis c282y/c282y (known as c282y homozygote), doctors recommend that all your siblings, parents and adult children get tested for the condition. […] If you have been diagnosed with genetic haemochromatosis c282y/h63d (known as compound heterozygote), we also recommend that family members should be tested.

• #45 Haemochromatosis – British Liver Trust

  https://britishlivertrust.org.uk/information-and-support/liver-conditions/haemochromatosis/

  Diagnostic technology has been developed specifically for iron-overloading disease. […] Treatment of haemochromatosis is simply aimed at removing iron from your body. […] During phlebotomy a unit of blood, usually 450 millitres (ml), is removed. […] After your course of treatment you will need to have further phlebotomies two to four times a year for the rest of your life. […] If you have a family history of haemochromatosis, you should see a medical professional as soon as you can. […] Genetic counselling can help you to better understand the likely occurrence of haemochromatosis in your family or explain the implications of any diagnosis.

• #46 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. […] You cant prevent the disease, but early diagnosis and treatment can avoid, slow or reverse organ damage. […] If you potentially have hemochromatosis, your healthcare provider will: […] Your healthcare provider may order: […] Diet changes and other treatments can help ease the symptoms of hemochromatosis. […] You cant prevent hemochromatosis, but you can get help controlling your iron levels. […] The outlook for hemochromatosis depends on the timing of diagnosis and treatment. […] But hemochromatosis is also a manageable disease. With early detection and treatment, you can survive and live a normal, healthy life. […] If you are diagnosed with hemochromatosis, you’ll need to have some blood withdrawn once a week to start. […] Talk to your healthcare provider if you have symptoms of hemochromatosis or a family history of it. Genetic testing can identify the disease early so you can live a long, healthy life.

• #47 Haemochromatosis | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/haemochromatosis

  Haemochromatosis tends to be under-diagnosed, partly because its symptoms are similar to those caused by a range of other illnesses. […] A simple blood test can establish whether a person is carrying the mutated HFE genes. […] A person with haemochromatosis is treated with venesection. […] If a person is diagnosed before significant symptoms arise, they can prevent organ damage and disease symptoms by maintaining iron in the normal range.

• #48 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. […] You cant prevent the disease, but early diagnosis and treatment can avoid, slow or reverse organ damage. […] If you potentially have hemochromatosis, your healthcare provider will: […] Your healthcare provider may order: […] Diet changes and other treatments can help ease the symptoms of hemochromatosis. […] You cant prevent hemochromatosis, but you can get help controlling your iron levels. […] The outlook for hemochromatosis depends on the timing of diagnosis and treatment. […] But hemochromatosis is also a manageable disease. With early detection and treatment, you can survive and live a normal, healthy life. […] If you are diagnosed with hemochromatosis, you’ll need to have some blood withdrawn once a week to start. […] Talk to your healthcare provider if you have symptoms of hemochromatosis or a family history of it. Genetic testing can identify the disease early so you can live a long, healthy life.

• #49 Hemochromatosis Workup: Approach Considerations, Transferrin Saturation, Serum Ferritin Studies

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

  The diagnosis of hemochromatosis is based on clinical features of the disease; these features include diffuse hyperpigmentation, hepatomegaly, and diabetes mellitus accompanied with biochemical abnormalities of iron metabolism and genotypic investigation. […] Perform early genetic testing or liver biopsy to avoid the complications of hemochromatosis. […] Examination of HFE mutations is pivotal for diagnosis of hemochromatosis; the discovery of the HFE gene allows easy differentiation of hereditary hemochromatosis from other forms of hepatic iron overload, including dysmetabolic hepatic siderosis. […] Measuring serum iron has no value in the diagnosis, but measuring transferrin saturation is necessary. […] The American College of Physicians found insufficient evidence to recommend for or against the use of transferrin saturation and serum ferritin levels to help identify the early stages of hereditary hemochromatosis.

• #50 Testing for HFE-related haemochromatosis – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/testing-for-hfe-related-haemochromatosis.html

  Patients with suspected iron overload should first have their serum ferritin and fasting transferrin saturation measured. HFE genotyping should be carried out in all patients with an elevated serum ferritin and transferrin saturation. Diagnosis of HFE-haemochromatosis should not be based on C282Y homozygosity alone, but requires evidence of increased hepatic iron stores.

• #51 Hemochromatosis: Practice Essentials, Background, Pathophysiology

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

  Clinical suspicion and early diagnosis are essential in hemochromatosis. The goal of therapy in patients with iron overload disorders is to remove the iron before it can produce irreversible parenchymal damage. […] Once diagnosed, hemochromatosis is treated by phlebotomy to rid the body of excess iron and to maintain normal iron stores. Phlebotomy remains the sole recommended treatment for hereditary hemochromatosis and should be undertaken in a case-specific manner.

• #52 Diagnosis of hemochromatosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9867744/

  If untreated, hemochromatosis can cause serious illness and early death, but the disease is still substantially under-diagnosed. The cornerstone of screening and case detection is the measurement of serum transferrin saturation and the serum ferritin level. Once the diagnosis is suspected, physicians must use serum ferritin levels and hepatic iron stores on liver biopsy specimens to assess patients for the presence of iron overload. Liver biopsy is also used to establish the presence or absence of cirrhosis, which can affect prognosis and management. A DNA-based test for the HFE gene is commercially available, but its place in the diagnosis of hemochromatosis is still being evaluated. Currently, the most useful role for this test is in the detection of hemochromatosis in the family members of patients with a proven case of the disease. It is crucial to diagnose hemochromatosis before hepatic cirrhosis develops because phlebotomy therapy can avert serious chronic disease and can even lead to normal life expectancy.

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