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Hemochromatosis (a.k.a. Iron Overload)

Tom Deloughery, MD and Rob Orman, MD
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Phlebotomy might be an old school therapy, but it’s still the best for hemochromatosis.

 

Pearls:

  • Though its penetrance is low (manifesting symptoms in only 10-30% of homozygotes), hemochromatosis is the most common genetic disease in Caucasians.  

  • Common initial symptoms are fatigue and arthralgias.

  • Screening is a two step process.  If the ferritin is elevated, check for an elevated iron saturation.

  • For patients with a high ferritin and iron saturation, testing for the C282Y mutation of the HFE gene is recommended.  Results may benefit family screening.

  • Therapeutic phlebotomy is the most effective treatment for hemochromatosis.  It should be commenced when the ferritin is above normal and continued weekly until the ferritin decreases to 50 ng/mL.

 

  • Hereditary hemochromatosis (HH) is the most common genetic disease affecting Caucasians.  Approximately 1 in 10 Caucasians carry one of the genetic defects associated with hemochromatosis (though most are asymptomatic)  Hemochromatosis causes excess absorption of iron from the digestive tract.  With time, the excess iron can accumulate in body tissues, especially the liver, pancreas and heart.

  • Early signs and symptoms of hemochromatosis can be nonspecific.  Common ones include fatigue, weakness, and arthritis.  Men may also present with loss of libido and impotence which is due to associated low testosterone levels.  

  • Laboratory testing for suspected hemochromatosis is a two step process.

    • The initial screening test is a serum ferritin.  A ferritin of over 200 ng/mL in women and over 300 ng/mL in men warrants further testing to rule out the disease.  By the time someone is having end-organ damage due to hemochromatosis, the ferritin is typically much higher, over 800 ng/mL in women and over 1000 ng/mL in men.  

    • The second step is getting an iron saturation, which is almost always elevated in hemochromatosis (greater than 42% in women and greater than 50% in men.)  A patient who has an elevated ferritin but a low iron saturation is more likely to have an inflammatory process, fatty liver, nonalcoholic steatohepatitis, type 2 diabetes, or other issues.  

  • Is it worth getting genetic studies on everyone who is diagnosed with hemochromatosis?  Yes, as it is helpful for family screening.  By diagnosing this disease earlier in family members before they are symptomatic, there is an opportunity to keep their iron under control through phlebotomy and prevent end-organ damage .  

  • Genetic testing for hemochromatosis, simplified.

    • The gene that is most commonly mutated in hereditary hemochromatosis (HH) is called HFE.   When the gene is mutated, too much iron absorption occurs.

    • The classic mutation is the C282Y, and this is the only test that Deloughery orders.  Other genetic mutations of HFE include H63D and S65C.  

  • Checking a response in the ferritin level to phlebotomy can also help diagnose hemochromatosis.  It is becoming common for insurance companies to deny coverage of genetic testing for HH, arguing that a patient with an elevated ferritin and iron saturation with warrant phlebotomy regardless of the genetic test results.  In these cases, a trial of phlebotomy can help determine if they have hemochromatosis.  In people with elevated ferritin levels who do not have hemochromatosis, a ferritin will typically return to normal after only 3-4 sessions of phlebotomy.  On the other hand, people with hemochromatosis will require 15 or more weekly sessions of phlebotomy before achieving a normal ferritin level.  This response to phlebotomy can be therapeutic as well as diagnostic.

  • What monitoring is recommended for a patient with hereditary hemochromatosis whose ferritin is not yet elevated?  

    • For homozygotes, check a ferritin once a year.  The penetrance is surprisingly low for these patients, especially for women.  It is between 10 and 30%.  

    • For a heterozygote who has a ferritin is in the 100’s, check once a year.  If the ferritin is lower, it is reasonable to recheck every several years.

  • When do you start therapeutic phlebotomy for a patient with hemochromatosis?  Deloughery recommends phlebotomy as soon as the ferritin is above normal.  He continues phlebotomy until the ferritin is down to 50 ng/mL and then restarts when it returns to a value above 100 ng/mL.

  • Should family members of patients with hereditary hemochromatosis be screened?  Yes, but only screen relatives of patients who are homozygous for the genetic mutation.  The gene frequency is 1 in 10 in the general population of Caucasians.   

  • How should patients with HH be monitored, to look for evidence of disease progression?  

    • A baseline echocardiogram, ECG, liver ultrasound, liver function tests, and hemoglobin A1C can be considered on all patients.  If these tests are normal, they do not need to be repeated as long as the patient is being treated with phlebotomy.

  • The mainstay of treatment for HH is phlebotomy.  How is this done?

    • One unit of blood, or 500 mls, is removed per week.

    • A ferritin that was initially in the thousands or high hundreds is checked once a month until it reaches 200 ng/mL.  At that point, the frequency of testing increases to every 1-2 weeks until it is down to 50 ng/mL.  For some patients, this can take a many months.

    • At that point, phlebotomy is discontinued and ferritin levels are checked every 3-4 months.

    • When the ferritin goes above 100 ng/mL, phlebotomy is restarted.  Some patients can go years before needed to restart.

    • Surprisingly, phlebotomy does not lead to anemia in these patients.  When the iron is removed, the body has a mechanism to produce more blood.

  • Can patients with hemochromatosis be blood donors?  Yes.  Some patients with HH who require phlebotomy will try to save money by donating their blood to the American Red Cross.  The blood is iron-rich and safe to be used for transfusion.  However, the patients will still need to have their ferritins checked periodically by their primary care physician or hematologist.  

  • What other treatments are available for hemochromatosis?

    • Chelation therapy with drugs that tightly bind to iron and remove it from the body have been used, but they are not nearly as effective as phlebotomy.  Plus, they are toxic and costly.

  • Are there dietary considerations for hemochromatosis?

    • There is no evidence that eating iron-rich foods, such as red meat, worsens the condition.

    • Tea, which can inhibit iron absorption, may be helpful.

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There's a High Pressure System in the Lungs Today Full episode audio for MD edition 182:19 min - 86 MB - M4AHippo Primary Care RAP November 2015 Summary 733 KB - PDF

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