Causes
Hemochromatosis can be either hereditary (primary) or acquired (secondary). Hereditary hemochromatosis is the most common form and is caused by genetic defects.- Hereditary Hemochromatosis (Primary Hemochromatosis):
- Caused by mutations in genes that control iron absorption. The most common mutation is in the HFE gene (C282Y and H63D mutations).
- If you inherit two copies of the mutated gene (one from each parent), you are at risk of developing iron overload.
- If you inherit one copy, you are a carrier but typically do not develop the condition, though you might have slightly elevated iron levels.
- Secondary Hemochromatosis (Acquired Hemochromatosis):
- Frequent Blood Transfusions: For conditions like thalassemia, sickle cell anemia, or myelodysplastic syndromes, where patients receive many transfusions, each unit of blood contains iron that the body cannot easily excrete.
- Excessive Iron Supplementation: Taking too many iron pills over a long period.
- Certain Liver Diseases: Such as chronic hepatitis C, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH), which can impair iron regulation.
- Rare Metabolic Disorders: Like aceruloplasminemia or atransferrinemia, which affect iron metabolism.
Symptoms
Symptoms of hemochromatosis often develop slowly and may not appear until middle age or later, after significant iron has accumulated. Early symptoms can be vague and mimic other conditions.- Joint Pain: Especially in the knuckles of the first two fingers.
- Fatigue: Persistent and unexplained tiredness.
- Weakness.
- Abdominal Pain: Often in the upper right quadrant.
- Loss of Libido (Sex Drive).
- Impotence (Erectile Dysfunction) in Men.
- Irregular Periods or Early Menopause in Women.
- Heart Problems:
- Irregular heartbeats (arrhythmias).
- Cardiomyopathy (enlarged heart).
- Heart failure.
- Liver Disease:
- Enlarged liver (hepatomegaly).
- Cirrhosis (scarring of the liver), which can lead to liver failure or liver cancer.
- Diabetes: Due to iron damage to the pancreas.
- Skin Changes: Gray or bronze skin color (often called "bronze diabetes").
- Hair Loss.
- Memory Fog or Mood Changes.
Diagnosis
Diagnosis of hemochromatosis involves blood tests to check iron levels, genetic testing, and sometimes imaging or biopsy to assess organ damage.- Blood Tests:
- Serum Transferrin Saturation: Measures the amount of iron bound to transferrin, a protein that transports iron in the blood. A high percentage (over 45%) suggests iron overload.
- Serum Ferritin: Measures the amount of iron stored in the body. High ferritin levels indicate excessive iron stores.
- Genetic Testing: If blood tests suggest iron overload, genetic testing for HFE mutations (C282Y and H63D) confirms hereditary hemochromatosis.
- Liver Biopsy: A small sample of liver tissue is removed and examined under a microscope to measure iron content and assess for liver damage (e.g., cirrhosis). This is less common now with advanced imaging.
- Imaging Tests:
- MRI (Magnetic Resonance Imaging): Can be used to quantify iron levels in the liver, heart, and other organs non-invasively.
- CT Scan (Computed Tomography): May be used to assess organ damage.
- Liver Function Tests (LFTs): To check for signs of liver damage.
Treatment
The primary treatment for hemochromatosis aims to reduce iron levels in the body and prevent or minimize organ damage. Early diagnosis and treatment are crucial.- Phlebotomy (Blood Removal):
- The most common and effective treatment. It involves regularly removing blood from the body, similar to donating blood.
- Initially, blood may be removed frequently (e.g., once a week) until iron levels return to normal.
- Once iron levels are normalized, maintenance phlebotomy is performed less frequently (e.g., every 2-3 months) to keep levels in the healthy range.
- Chelation Therapy:
- Used for people who cannot undergo phlebotomy (e.g., due to anemia, certain heart conditions, or severe iron overload).
- Medications are given orally or by injection that bind to excess iron, allowing it to be excreted in urine or stool. Examples include deferoxamine, deferiprone, and deferasirox.
- Dietary Modifications:
- Avoid iron supplements and multivitamins containing iron.
- Avoid vitamin C supplements: Vitamin C enhances iron absorption, so it should not be taken at the same time as iron-rich meals or supplements.
- Limit iron-rich foods: Such as red meat, especially organ meats.
- Avoid raw shellfish: Can contain bacteria that thrive in iron-rich environments and cause serious infections in people with hemochromatosis.
- Avoid alcohol: Alcohol can increase iron absorption and is toxic to the liver, exacerbating liver damage in hemochromatosis.
- Treatment of Complications:
- Medications for diabetes, heart conditions, or joint pain.
- Management of cirrhosis or liver cancer if they develop.
- Genetic Counseling: For family members of individuals with hereditary hemochromatosis to understand their risk and consider testing.
Living With Hemochromatosis
Hemochromatosis is unusual among chronic conditions: treatment is simple, well tolerated, and prevents nearly all complications when started before organ damage occurs. What matters over decades is keeping up with maintenance, protecting the liver, and making sure relatives are tested.
What phlebotomy is like
Each session removes about a pint of blood, much like a donation, and takes under an hour. Eating beforehand, drinking extra fluid that day, and skipping strenuous exercise afterward prevent most lightheadedness. Blood counts are checked before each session so iron is not removed faster than the marrow tolerates, and ferritin is tracked until it reaches the target range, when sessions spread out to a few times a year. Energy often improves during the first year, and some blood centers now accept hemochromatosis blood for donation.
Protecting the liver
Iron and alcohol damage the liver together far faster than either alone, so alcohol is kept minimal or avoided; our alcohol and health guide explains the reasoning. Hepatitis A and B vaccination, a one-time hepatitis C screen, and attention to fatty liver disease matter for the same reason. Anyone found to have cirrhosis at diagnosis remains at elevated risk of liver cancer even after iron is normalized and needs ultrasound surveillance every six months for life.
Diet without obsession
Once phlebotomy is regular, a normal healthy diet is fine; one serving of red meat adds far less iron than one session removes. What matters is avoiding iron and vitamin C supplements, limiting alcohol, and never eating raw shellfish, because Vibrio bacteria in Gulf waters thrive on excess iron and can cause overwhelming infection in people with iron overload. Our Vibrio safety article covers oysters, wounds, and the local season.
The organs that are checked
Blood sugar is monitored because iron in the pancreas causes diabetes; an ECG and sometimes an echocardiogram look for cardiomyopathy and rhythm problems; and men are asked about low testosterone, which iron in the pituitary causes and which is treatable. Joint damage in the knuckles and hips does not reverse with phlebotomy and is managed like osteoarthritis, which is one more reason to treat early.
Testing the family
Every parent, sibling, and adult child of someone with hereditary hemochromatosis should have transferrin saturation, ferritin, and HFE gene testing, since a sibling has a one-in-four chance of carrying both mutations. Our family medical history article explains how to start that conversation, and our hematology team manages phlebotomy and monitoring. The NIDDK and MedlinePlus publish patient guidance on testing and treatment.
If a relative has hemochromatosis, or your ferritin has come back high and nobody has explained what to do next, schedule a visit.