Training & Education - Course Summary
- The disease, hemochromatosis, a disorder of iron metabolism, occurs as a result of excess iron accumulation in tissues and organs.
- Early detection of iron overload and hemochromatosis treatment can delay or prevent irreversible complications and prolong life.
- The diagnosis of hemochromatosis is often missed, especially when the disease is in its early stages.
- Early non-specific symptoms of hemochromatosis (i.e., fatigue, arthralgias, weakness, weight loss, abdominal pain) resemble various other disease processes.
- Health care professionals therefore need to maintain a high index of suspicion for patients who have early non-specific hemochromatosis symptoms.
- Phlebotomy, the treatment of choice, is relatively easy, safe, and inexpensive.
- Iron overload is the accumulation of excess iron in body tissues.
- Once iron is absorbed, there is no physiologic mechanism for excretion of excess iron from the body other than blood loss i.e., pregnancy, menstruation or other bleeding.
- Iron is bound and transported in the body via transferrin and stored in ferritin molecules.
- The liver and heart are especially vulnerable.
- Hemochromatosis is a disease that occurs as a result of significant iron overload. It can have genetic (majority of cases) or non-genetic causes.
- Men thus tend to become symptomatic in middle age (40s) and women who stop menstruating develop symptoms about 15 years later.
HFE Gene Mutations
- HFE gene mutations can lead to iron overloading.
- Hereditary hemochromatosis is the genetic disease that results from significant iron overload.
- The majority of hereditary hemochromatosis (also known as Type 1 Hemochromatosis) is associated with homozygous mutations in the HFE gene.
- People with HFE mutations absorb a few extra milligrams of iron per day. Over decades, this leads to iron overloading that can lead to disease.
- Reported U.S. population prevalence estimates of iron overloading (based on random non-fasting elevated TS values) range from 1% to 6%.
- A lower percentage of people who initially have a random elevated TS also have persistently elevated TS: estimates range from 35% to 50%.
- An even lower percentage of people with persistently elevated TS measures also have elevated serum ferritin values.
- Thus, the proportion of people who will develop clinical signs and symptoms of hemochromatosis is even lower than the proportion of people with elevated SF values.
HFE Gene Mutations
- Two HFE gene mutations, C282Y and H63D, account for the majority of hereditary hemochromatosis cases; C282Y is most common.
- Hereditary hemochromatosis is inherited in an autosomal recessive pattern.
HFE Genotype Frequencies
- The population prevalence of HFE mutations depends on race and ethnicity but is most prevalent among persons of European origin and descent.
- Of people with HFE gene mutations, only a subset will develop an elevated TS. Of those with an elevated TS, only a subset will develop an elevated SF. Of those with an elevated SF, only a subset will develop hemochromatosis symptoms. Of those with symptoms, only a subset will develop clinical signs consistent with hemochromatosis.
- Most clinicians reserve the hemochromatosis diagnosis for patients whose signs and symptoms are clearly referable to documented iron overload as reflected by serum iron testing measurements.
- Iron status testing is more clinically relevant than genetic testing for identifying those who have hemochromatosis.
- At this time, CDC does not recommend population screening for HFE gene mutations because of the uncertainty about what proportion of people with HFE gene mutations will develop hemochromatosis.
- The iron accumulation rate and the frequency and severity of clinical symptoms vary widely and may be dependent on factors such as age, gender, and diet.
- The most commonly associated early hemochromatosis symptoms are non-specific and may include:
- Weight loss.
- Abdominal pain.
- As iron accumulation progresses, patients may also experience:
- Symptoms of gonadal failure.
- For example, amenorrhea, early menopause, loss of libido, impotence.
- Shortness of breath/dyspnea.
- Maintain a high index of suspicion of hemochromatosis for patients with early signs or symptoms of this disease.
- Iron accumulates in the parenchymal cells of several organs; the liver is a major site followed by the heart and pancreas.
- The liver is usually the first organ to be affected, but signs of organ damage occur in the later stages of the disease.
Primary Disorders Associated with Advanced Hemochromatosis
- Most advanced hemochromatosis complications are also common primary disorders.
- A hemochromatosis diagnosis can be missed even in advanced stages unless looked for specifically.
- Biochemical testing for iron status is recommended for patients with:
- Symptoms or signs suggestive of hemochromatosis.
- Porphyria, hepatitis or other liver diseases.
- Abnormal blood tests consistent with hemochromatosis.
- Evaluation for other causes of these medical problems should also be performed.
- Testing is also recommended for family members of diagnosed patients.
- Recommended laboratory iron tests for the workup of a patient you suspect may have hemochromatosis are:
- Fasting transferrin saturation test (TS).
- Serum ferritin test (SF).
- Transferrin saturation (TS).
- Fasting values >45% should be followed by a serum ferritin test and additional workup.
- Serum ferritin (SF).
- Values >;200 ng/mL for premenopausal females OR >300 ng/mL for postmenopausal females and males indicate iron overload; phlebotomy treatment is warranted in the absence of other causes.
- SF values can be elevated with liver disease, inflammation, and neoplasm.
- Confirmation of iron overload is typically required:
- Most health care providers consider quantitative phlebotomy the confirmatory test of choice.
- Genotyping for HFE mutations can provide additional confirmatory evidence that a patient has hereditary hemochromatosis.
- Many authorities once considered liver biopsy an essential diagnostic test, but it is now used more often as a prognostic, rather than a diagnostic, test.
- Therapeutic phlebotomy is the preferred treatment for reducing iron stores in hemochromatosis patients.
- For a patient who has no evident tissue or organ damage, proper disease management may result in normal long-term outcome and life expectancy.
- Clinicians must design phlebotomy treatment regimens that are individualized to each patient and account for age, gender, weight, health, and likelihood of compliance.
- Serum ferritin levels should be measured after each additional one or two phlebotomy treatments once the value is less than or equal to 100 ng/mL.
- Careful monitoring of each patient throughout treatment is imperative. If treatment is too aggressive, anemia may result.
- Continued lifetime monitoring is key to appropriate management.
- Phlebotomy should be performed throughout a patient’s life to keep the ferritin level between 25 and 50 ng/mL.
- Download a print-friendly "Phlebotomy Information for Patients with Hemochromatosis."
- Hemochromatosis cannot be treated by diet alone.
- The following dietary modifications for patients are suggested:
- Avoid iron supplements.
- Read the label of multivitamins to make sure they do not contain iron.
- Limit vitamin C supplementation to 500 mg/day.
- Avoid eating raw shellfish.
- Avoid more than moderate alcohol consumption. Patients with liver damage should avoid alcohol.
- Download a print-friendly "Diet information for patients with hemochromatosis."
Patients and Their Families
- A hemochromatosis diagnosis identifies a patient who needs treatment and a family potentially at risk.
- Encouraging hemochromatosis patients to urge family members to have biochemical tests for iron overload, (fasting transferring saturation and serum ferritin), is an important disease prevention opportunity.
- Download and print on your letterhead information for patients and their families:
Genetic testing in families with HFE-associated hemochromatosis can be particularly useful for determining:
- Who is NOT at increased risk: A family member who has no HFE mutations has the same risk of developing hemochromatosis as the general population.
- If iron overloading is genetic: In a person with hemochromatosis, finding two HFE mutations confirms that iron overloading is genetic.
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- Centers for Disease Control and Prevention
National Center on Birth Defects and Developmental Disabilities
Division of Blood Disorders
1600 Clifton Road
Atlanta, GA 30333
TTY: (888) 232-6348
- Contact CDC-INFO