OVERVIEW

What is hemochromatosis?

Hemochromatosis, also known as iron overload disorder or hemosiderosis, is a disease caused by excessive iron accumulation in the body. Excess iron can deposit in organs such as the liver, pancreas, heart, kidneys, spleen, and skin, leading to skin pigmentation, hepatomegaly, cirrhosis, diabetes, cardiomegaly, arrhythmia, heart failure, and other complications. The iron levels in patients with hemochromatosis can be 50 to 100 times higher than those in healthy individuals.

Currently, there is no cure for this disease, but early treatment can prevent or delay the onset of complications. Without timely diagnosis and treatment, advanced stages of the disease may lead to complications such as cirrhosis, liver cancer, cardiomegaly, arrhythmia, heart failure, and secondary diabetes, severely affecting quality of life.

What are the types of hemochromatosis?

Hemochromatosis can be divided into two main categories: primary hemochromatosis (also known as "hereditary hemochromatosis") and secondary hemochromatosis. The former is related to familial inheritance, while the latter has various causes but is not hereditary.

Is hemochromatosis common?

It is uncommon in China.

Hereditary hemochromatosis is relatively common among Caucasians, with a higher prevalence in males, often diagnosed between the ages of 40 and 60. However, in China, hereditary hemochromatosis is considered a rare disease, and due to the limited number of cases, its exact incidence rate remains unquantified.

SYMPTOMS

What are the symptoms and manifestations of hemochromatosis?

Primary hemochromatosis has an insidious onset and progresses slowly. In the early stages, symptoms may include fatigue, weight loss, skin pigmentation, abdominal pain, and joint pain—common manifestations that may not raise immediate concern. Without timely diagnosis and treatment, advanced stages can lead to complications such as cirrhosis, liver cancer, cardiomegaly, arrhythmias, heart failure, and secondary diabetes, resulting in diverse clinical presentations.

• Skin pigmentation: Most noticeable in sun-exposed areas (face, neck, hands), external genitalia, and scars, appearing bronze or slate-gray. A few patients may also develop pigmentation in the conjunctiva and oral mucosa.
• Hepatomegaly: Early-stage liver enlargement may be asymptomatic. As the disease progresses, symptoms like right upper abdominal pain, fatigue, hair loss, and weight loss may occur. Advanced stages present with cirrhosis-related signs, such as edema, splenomegaly, gynecomastia (in men), hypogonadism, spider angiomas, and telangiectasia. Cirrhosis is one of the leading causes of death in hemochromatosis.
• Secondary diabetes: Symptoms include polydipsia, polyuria, polyphagia, weight loss, and fatigue.
• Cardiac diseases: Such as cardiomyopathy, cardiomegaly, arrhythmias, and heart failure, manifesting as chest tightness, palpitations, dyspnea, and edema. Cardiac complications are another major cause of mortality in hemochromatosis.
• Endocrine disorders: Typically presenting as hypogonadism—testicular atrophy, loss of facial hair, and erectile dysfunction in men, or menstrual irregularities and infertility in women.
• Osteoarticular lesions: Joint damage often first affects the metacarpophalangeal joints of the index and middle fingers, but may also involve knees, hips, shoulders, wrists, and ankles, causing pain, deformities, and osteoporosis.

Secondary hemochromatosis shares similar clinical features with the primary form, though some pediatric patients may exhibit growth retardation. Symptoms are rare in cases caused solely by excessive blood transfusions.

What complications can hemochromatosis cause?

Cirrhosis, liver cancer, diabetes, cardiomyopathy, arrhythmias, heart failure, hypopituitarism, joint deformities, osteoporosis, etc.

CAUSES

What are the causes of hemochromatosis?

• Primary hemochromatosis: It is related to familial inheritance and is also called "hereditary hemochromatosis." Due to genetic defects, the small intestine absorbs excessive iron, even when the body's iron levels are already too high, the absorption does not decrease.
• Secondary hemochromatosis: Secondary hemochromatosis is not hereditary but occurs as a result of various disease conditions, such as repeated hemolysis, long-term excessive blood transfusions, excessive iron intake, chronic alcoholism, chronic liver disease, aplastic anemia, etc.

Is hemochromatosis hereditary?

Primary hemochromatosis is hereditary.

Primary hemochromatosis (also called "hereditary hemochromatosis") is an autosomal recessive genetic disorder.

The characteristics of autosomal recessive inheritance are:

• If a patient marries someone with a normal genotype, all their children will be normal;
• If a patient marries a "normal" carrier (with one defective gene), their children have a 50% chance of being affected;
• If two "normal" carriers marry, their children have a 25% chance of being affected;
• If two patients marry, all their children will be affected, with equal chances for boys and girls.

Is hemochromatosis contagious?

No.

DIAGNOSIS

What tests are needed for hemochromatosis?

• Routine iron tests: Serum iron levels are elevated to over 200 μg/dL, averaging around 250 μg/dL, with transferrin iron saturation reaching 70%–100%. Plasma ferritin often exceeds 500 μg/L. Bone marrow smears or biopsies show significantly increased hemosiderin. Urinalysis and skin biopsies also reveal hemosiderin, with the latter additionally showing increased melanin.
• For atypical cases, a desferrioxamine test may be performed: Desferrioxamine is an iron chelator that binds iron and promotes its excretion in urine. The patient first takes vitamin C (200 mg daily for 7 days), followed by an intramuscular injection of desferrioxamine (10 mg per kg of body weight). A 24-hour urine iron excretion measurement is then taken, typically exceeding 5 mg or 10 mg (normal value is ≤ 2 mg).
• Liver biopsy: A small liver tissue sample is examined under a microscope to confirm hemochromatosis.
• CT or MRI scans: These can detect iron deposition in the liver and heart, aiding in the diagnosis of hemochromatosis. They may also reveal cirrhosis or liver cancer.
• Genetic testing: If necessary, genetic testing can be conducted to diagnose hereditary hemochromatosis.

Which diseases share similar symptoms with hemochromatosis?

Since hemochromatosis can lead to cirrhosis, diabetes, and heart disease in its advanced stages, it must be differentiated from these conditions when they occur independently. Routine iron tests can help distinguish them initially.

TREATMENT

Which department should I visit for hemochromatosis?

Hematology.

How is hemochromatosis treated?

Currently, hemochromatosis cannot be cured and requires long-term treatment. Common treatment measures include removing excess iron from the body and providing supportive therapy for damaged organs.

Once diagnosed with hemochromatosis, treatment should begin immediately to potentially reverse organ damage, improve quality of life, and prolong survival.

Common treatment methods are as follows:

Removing excess iron from the body:

• Phlebotomy: Since most iron is stored in the blood, removing blood can reduce iron levels. Typically, 400–500 ml of blood is removed per session, 1–2 times per week. During treatment, hemoglobin, serum iron, and ferritin levels should be monitored. When ferritin drops to 50–100 ng/ml, frequent phlebotomy can be paused, followed by maintenance therapy of 500 ml every 3–4 months to keep ferritin within the 50–100 ng/ml range.
• Erythrocytapheresis: A medical procedure that removes red blood cells from the blood and returns the plasma to the patient. This also reduces excess iron while minimizing the frequency and side effects of phlebotomy.
• Iron chelators: Used only for patients who cannot undergo phlebotomy, these drugs prevent or reverse iron deposition in organs. The commonly used drug is deferoxamine, administered via intravenous, intramuscular, or subcutaneous injection.

Supportive therapy for damaged organs:

• Diabetes: Blood sugar can be controlled through phlebotomy, dietary adjustments, and insulin injections. Secondary hemochromatosis makes blood sugar harder to manage.
• Heart disease: Arrhythmias may improve after iron removal. Treatment methods align with standard cardiac disease management.
• Endocrine dysfunction: Treated by supplementing deficient hormones (e.g., testosterone).
• Bone and joint disease: Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce inflammation and pain. Severe cases may require surgery.
• Liver cirrhosis: End-stage cirrhosis may require a liver transplant, but excess iron must first be removed to prevent recurrence.

What should I pay attention to during hemochromatosis treatment?

After phlebotomy, intravenous fluids or increased water intake are needed to restore blood volume. Avoid strenuous exercise for 24 hours.

Can hemochromatosis be fatal?

Possibly.

Hemochromatosis can lead to death, typically due to complications such as advanced cirrhosis, liver cancer, diabetes, or cardiomyopathy, which may occur in late-stage patients.

Early diagnosis and treatment can prevent these severe complications. If treatment begins before cirrhosis or diabetes develops, hemochromatosis has minimal impact on lifespan.

DIET & LIFESTYLE

What dietary precautions should be taken for hemochromatosis?

• Balanced diet: Eat more vegetables and fresh fruits (except citrus fruits and fresh juices).
• Reduce high-iron foods: Red meats (pork, beef, lamb) and seafood contain relatively high iron levels and can be replaced with freshwater fish and poultry.
• Choose appropriate beverages: Drinking tea and coffee helps reduce iron intake; avoid or limit alcohol consumption as it promotes iron absorption, worsens cirrhosis, and increases liver cancer risk; avoid fresh juices during meals, as their high vitamin C content enhances iron absorption from food—opt to drink juices between meals.
• Avoid additional iron and vitamin C supplements: Refrain from taking iron or vitamin C-containing supplements, multivitamins, etc.
• Ensure seafood is clean and hygienic: Hemochromatosis patients are prone to certain bacterial infections, which may lead to severe sepsis, so avoid undercooked seafood.

Does hemochromatosis affect fertility?

Possibly.

If hemochromatosis is poorly controlled, it may impact fertility, potentially causing infertility, miscarriages, stillbirths, or preterm births. Even if the condition is stable, it's advisable to consult a doctor before pregnancy.

Additionally, hereditary hemochromatosis is a genetic disorder. Before planning pregnancy, genetic counseling (usually available at genetic medicine centers or hospital-affiliated genetic clinics) is recommended to assess potential risks to offspring.

Does hemochromatosis affect daily activities like exercise, high-altitude travel, or flying?

Possibly.

If hemochromatosis is poorly controlled, strenuous exercise and high-altitude travel are not advisable. Consult a doctor before flying for relevant precautions.

PREVENTION

How to Prevent Hemochromatosis?

• Primary Hemochromatosis: Primary hemochromatosis is a genetic disorder and cannot be easily prevented. If someone is diagnosed with primary hemochromatosis, their first-degree relatives (parents, children, and siblings) can undergo screening for early diagnosis and treatment. In the early stages of hemochromatosis, phlebotomy therapy often yields good results.

• Secondary Hemochromatosis: Secondary hemochromatosis results from various underlying conditions, such as recurrent hemolysis, long-term excessive blood transfusions, excessive iron supplementation, prolonged consumption of iron-rich foods, or alcoholism. Preventive measures include treating the underlying condition promptly, adjusting inappropriate iron supplementation, avoiding high-iron diets, and abstaining from alcohol.