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Hemochromatosis What Is It?
Hereditary hemochromatosis (HH), also known as iron overload disease or "genetic iron poisoning", is the most common genetic disease in the U.S.A. according to the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. One in 8 are "silent carriers" of the single HH gene mutation and 1 in 100-200 have the double mutation putting them at high risk for developing full blown HH. HH can affect men, women and children at any age. Most of the 33 million Americans who have the HH gene mutation don’t know it but it can be diagnosed easily and quickly.
Do you or anyone in your family (living/deceased) have (or have a family history of) these symptoms or risk factors?
Arthritis
Joint pain/Replacement
Diagnosis of Fibromyalgia/Chronic Fatigue Syndrome (CFS)
Anemia
Hypothyroidism
Impotence/Early menopause / Irregular periods
Infertility /hysterectomy/no children
Diabetes mellitus /High blood sugar
Darkening of the skin without exposure to the sun
Heart Disease/Heart Attack
Stroke
Irregular heartbeat
bypass surgery
Hair loss
Weight loss
Set off airport metal detectors for no apparent reason
Ancestry of Celtic (Irish/Scottish/Welsh) British/Northern European origin
Liver disease/hepatitis/cirrhosis/primary liver cancer/elevated liver enzymes
enlarged liver/yellow skin & eyes (jaundice)
dark urine
red palms/Abdominal pain
Liver and/or heart transplant.
Ask your medical team for these HH blood tests by name: serum iron, TIBC (total iron binding capacity), and serum ferritin. Danger zone: % saturation greater than > 40% and/or ferritin greater than > 150 ng/mL. Ask for DNA testing by name for the Cys282Y & His63D mutations for both children & adults which will assess genetic risk for HH before damage occurs. Treatment is simple: bloodletting identical to a blood donation.
Q: What are the symptoms of iron overload, hemochromatosis?
A: Patients can have iron overload and NOT have symptoms (asymptomatic) and that is the best time to diagnose the patient. Many doctors have been taught to look for "signs and symptoms" of HH but by the time symptoms appear, it is often too late to save the patient's life. Iron overload and storage in vital body organs can damage and may cause:
chronic fatigue (the most common complaint by patients);
cirrhosis/cancer of the liver (with or without a history of alcohol use);
arthritis/joint pain;
impotence/sterility/infertility; early menopause/irregular menses;
hair loss;
diabetes (bronze diabetes, a darkening, graying of the skin not caused by sun exposure);
cancer (cancer thrives on iron);
abdominal pain/swelling;
weight loss;
frequent colds/flu/infections, compromised immune system;
headaches;
hypothyroidism;
heart irregularities/heart failure/heart attack (especially in younger men);
cirrhosis of the liver (with or without a history of alcohol use);
hepatoma/liver cancer (the leading cause of death in HH);
premature death.
Anyone with any combination of these symptoms, or a family history of these symptoms, should be tested for HH immediately. But remember, two important facts: 1.) There can be numerous generations of "silent carriers" of the mutation who never become ill and live to old age thereby giving a "false security" that HH doesn't "run in the family" 2.) Some patients do not have symptoms until they are end stage and their lives cannot be saved. Early detection should be achieved through: 1.) Knowledge of genetic risk through DNA Testing 2.) Annual screening with serum iron, TIBC, and serum ferritin to assure that iron storage is not taking place.
Recommendations for genetic testing:
Investigations and diagnosis
This involves assessment of iron overload, genetics and organ damage. These tests need careful interpretation.
Initial investigations
Hemochromatosis What Is It?
Hereditary hemochromatosis (HH), also known as iron overload disease or "genetic iron poisoning", is the most common genetic disease in the U.S.A. according to the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. One in 8 are "silent carriers" of the single HH gene mutation and 1 in 100-200 have the double mutation putting them at high risk for developing full blown HH. HH can affect men, women and children at any age. Most of the 33 million Americans who have the HH gene mutation don’t know it but it can be diagnosed easily and quickly.
Do you or anyone in your family (living/deceased) have (or have a family history of) these symptoms or risk factors?
Arthritis
Joint pain/Replacement
Diagnosis of Fibromyalgia/Chronic Fatigue Syndrome (CFS)
Anemia
Hypothyroidism
Impotence/Early menopause / Irregular periods
Infertility /hysterectomy/no children
Diabetes mellitus /High blood sugar
Darkening of the skin without exposure to the sun
Heart Disease/Heart Attack
Stroke
Irregular heartbeat
bypass surgery
Hair loss
Weight loss
Set off airport metal detectors for no apparent reason
Ancestry of Celtic (Irish/Scottish/Welsh) British/Northern European origin
Liver disease/hepatitis/cirrhosis/primary liver cancer/elevated liver enzymes
enlarged liver/yellow skin & eyes (jaundice)
dark urine
red palms/Abdominal pain
Liver and/or heart transplant.
Ask your medical team for these HH blood tests by name: serum iron, TIBC (total iron binding capacity), and serum ferritin. Danger zone: % saturation greater than > 40% and/or ferritin greater than > 150 ng/mL. Ask for DNA testing by name for the Cys282Y & His63D mutations for both children & adults which will assess genetic risk for HH before damage occurs. Treatment is simple: bloodletting identical to a blood donation.
Q: What are the symptoms of iron overload, hemochromatosis?
A: Patients can have iron overload and NOT have symptoms (asymptomatic) and that is the best time to diagnose the patient. Many doctors have been taught to look for "signs and symptoms" of HH but by the time symptoms appear, it is often too late to save the patient's life. Iron overload and storage in vital body organs can damage and may cause:
chronic fatigue (the most common complaint by patients);
cirrhosis/cancer of the liver (with or without a history of alcohol use);
arthritis/joint pain;
impotence/sterility/infertility; early menopause/irregular menses;
hair loss;
diabetes (bronze diabetes, a darkening, graying of the skin not caused by sun exposure);
cancer (cancer thrives on iron);
abdominal pain/swelling;
weight loss;
frequent colds/flu/infections, compromised immune system;
headaches;
hypothyroidism;
heart irregularities/heart failure/heart attack (especially in younger men);
cirrhosis of the liver (with or without a history of alcohol use);
hepatoma/liver cancer (the leading cause of death in HH);
premature death.
Anyone with any combination of these symptoms, or a family history of these symptoms, should be tested for HH immediately. But remember, two important facts: 1.) There can be numerous generations of "silent carriers" of the mutation who never become ill and live to old age thereby giving a "false security" that HH doesn't "run in the family" 2.) Some patients do not have symptoms until they are end stage and their lives cannot be saved. Early detection should be achieved through: 1.) Knowledge of genetic risk through DNA Testing 2.) Annual screening with serum iron, TIBC, and serum ferritin to assure that iron storage is not taking place.
- Investigations and diagnosis
- This involves assessment of iron overload, genetics and organ damage. These tests need careful interpretation. Assessment of iron stores?
- Patients with suspected iron overload should first receive measurement of fasting transferrin saturation and serum ferritin, and HFE genetic testing should be performed only in those with increased transferrin saturation.
- Serum ferritin is the most widely used biochemical test for iron overload. Serum ferritin is a very sensitive test for iron overload in haemochromatosis and normal serum concentrations essentially rule out iron overload.
- However, ferritin has low specificity, as elevated values can be the result of a range of inflammatory, metabolic, and neoplastic conditions such as diabetes mellitus, alcohol consumption, and hepatocellular or other cell necrosis.
- Serum iron concentration and transferrin saturation do not quantitatively reflect body iron stores and should therefore not be used alone as markers of tissue iron overload.Tests to exclude common causes of hyperferritinaemia: inflammation (check CRP), chronic alcohol consumption, liver cell necrosis (alanine aminotransferase), metabolic syndrome (blood pressure, BMI, triglycerides, and glucose), anaemia (haemoglobin, mean cellular volume and further tests depending on ethnic background - eg, testing for sickle cell disease).
- Other tests, including endocrine investigations, may be indicated, depending on the clinical situation.
- Investigations for other causes of abnormal liver function (eg, hepatitis serology) may be relevant.
- 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.
- Liver biopsy 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.
- Liver biopsy may still be indicated - eg, to show whether iron stores are increased or not, and in assessing liver fibrosis.
- MRI may be useful to detect and quantify hepatic iron excess and may also help to identify heterogeneous distribution of iron within the liver, differentiate parenchymal from mesenchymal iron overload, and to detect small iron-free neoplastic lesionsoms usually start between ages 30-50, but may begin earlier.
- Initial symptoms are usually vague and nonspecific - eg, fatigue, weakness, arthropathy affecting varus joints, nonspecific abdominal problems, erectile dysfunction and heart problems.
- HHC may be diagnosed incidentally - eg, following abnormal serum ferritin or LFTs.
- Symptoms of advanced disease include diabetes, bronzing of the skin, hepatomegaly and arthropathy, especially of the second and third metacarpophalangeal joints. Other presenting features of advanced disease include. Impotence, amenorrhoea or hypogonadism. Cirrhosis. Diabetes mellitus. Cardiac disease - arrhythmias or cardiomyopathy. Neurological or psychiatric symptoms - impaired memory, mood swings, irritability, depression.
Recommendations for genetic testing:
- General population: genetic screening for HFE-HC is not recommended, because disease penetrance is low and only in few C282Y homozygotes will iron overload progress.
- HFE testing should be considered in patients with unexplained chronic liver disease pre-selected for increased transferrin saturation.
- HFE testing could be considered in patients with:
- Porphyria cutanea tarda.
- Well-defined chondrocalcinosis.
- Hepatocellular carcinoma.
- Type 1 diabetes.
- HFE testing is not recommended in patients with unexplained arthritis or arthralgia or with type 2 diabetes.
Investigations and diagnosis
This involves assessment of iron overload, genetics and organ damage. These tests need careful interpretation.
Initial investigations
- Assessment of iron stores
- Patients with suspected iron overload should first receive measurement of fasting transferrin saturation and serum ferritin, and HFE genetic testing should be performed only in those with increased transferrin saturation.
- Serum ferritin is the most widely used biochemical test for iron overload. Serum ferritin is a very sensitive test for iron overload in haemochromatosis and normal serum concentrations essentially rule out iron overload.
- However, ferritin has low specificity, as elevated values can be the result of a range of inflammatory, metabolic, and neoplastic conditions such as diabetes mellitus, alcohol consumption, and hepatocellular or other cell necrosis.
- Serum iron concentration and transferrin saturation do not quantitatively reflect body iron stores and should therefore not be used alone as markers of tissue iron overload.
- Tests to exclude common causes of hyperferritinaemia: inflammation (check CRP), chronic alcohol consumption, liver cell necrosis (alanine aminotransferase), metabolic syndrome (blood pressure, BMI, triglycerides, and glucose), anaemia (haemoglobin, mean cellular volume and further tests depending on ethnic background - eg, testing for sickle cell disease) LFTs. Other tests, including endocrine investigations, may be indicated, depending on the clinical situation.
- Investigations for other causes of abnormal liver function (eg, hepatitis serology) may be relevant.
- Genetic testing
- 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.
- Liver biopsy:
- 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.
- Liver biopsy may still be indicated - eg, to show whether iron stores are increased or not, and in assessing liver fibrosis.
- MRI may be useful to detect and quantify hepatic iron excess and may also help to identify heterogeneous distribution of iron within the liver, differentiate parenchymal from mesenchymal iron overload, and to detect small iron-free neoplastic lesions.
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