Hemochromatosis (Iron Overload)

How iron overload happens

The body has no natural way to get rid of excess iron, so it controls iron by limiting how much the gut absorbs, using the hormone hepcidin. In hereditary hemochromatosis, faulty HFE (or other) genes lower hepcidin, so the gut absorbs 2 to 3 times more iron than needed. Over decades, iron accumulates in organs, where it causes oxidative damage and scarring.

Symptoms usually appear between ages 40 and 60 in men. Women tend to develop problems later, often after menopause, because menstruation and pregnancy remove iron.

Types and causes

Hereditary hemochromatosis

• HFE-related (type 1): the most common, especially homozygous C282Y (two copies). Compound C282Y/H63D causes milder overload, usually only with other factors such as alcohol or fatty liver. H63D alone rarely causes significant overload.
• Non-HFE types: rare juvenile forms (hemojuvelin, hepcidin genes) cause severe overload in young people; transferrin receptor 2 and ferroportin forms also exist.

Many people with two C282Y copies never develop organ damage; men are more likely to.

Secondary iron overload

Iron overload also occurs with repeated blood transfusions (for thalassemia, sickle cell disease, myelodysplastic syndrome), some anemias with ineffective red cell production, chronic liver disease and excessive iron supplements.

Symptoms

Early

• fatigue and weakness
• joint pain, especially in the second and third knuckles ("iron fist"), wrists, hips and knees
• abdominal pain in the upper right side
• low libido, erectile dysfunction, missed periods
• memory fog and low mood

Later, from organ damage

• Liver: enlarged liver, fibrosis, cirrhosis and liver cancer
• Pancreas: diabetes ("bronze diabetes")
• Heart: cardiomyopathy, heart failure and arrhythmias
• Skin: bronze or gray darkening
• Glands: low testosterone (hypogonadism), hypothyroidism
• Joints: arthritis resembling osteoarthritis and calcium pyrophosphate deposits
• Bones: osteoporosis

Diagnosis

1. Transferrin saturation: the best first test. A fasting level above about 45 percent suggests iron overload.
2. Serum ferritin: reflects iron stores. Ferritin can also be raised by inflammation, alcohol, fatty liver and metabolic syndrome, so it is interpreted with transferrin saturation.
3. HFE gene test: confirms hereditary hemochromatosis when both are raised.
4. Liver assessment: liver blood tests, ultrasound and elastography. A ferritin over 1,000 µg/L raises the risk of cirrhosis and may prompt a biopsy or further imaging.
5. MRI can measure iron in the liver and heart without a biopsy.
6. Other checks: blood sugar, heart tests, hormone levels, bone density.

Family screening

First-degree relatives (parents, siblings, children) of someone with HFE hemochromatosis should have iron studies and genetic testing, because each sibling has a 1 in 4 chance of inheriting two copies.

Treatment

Phlebotomy (therapeutic venesection)

Removing about 500 ml of blood, like a blood donation, takes iron out of the body because each unit contains about 200 to 250 mg of iron.

• Initial phase: usually weekly, as tolerated, until ferritin falls to about 50 to 100 µg/L. This can take months to more than a year.
• Maintenance: typically every 2 to 4 months for life, to keep ferritin in range.

In many places, blood removed from people with hemochromatosis can be donated.

Other treatments

• Iron chelation medicines (deferasirox, deferoxamine) for people who cannot have phlebotomy, such as those with anemia or secondary overload.
• Erythrocytapheresis, removing only red cells, in some centers.
• Managing complications: diabetes treatment, heart failure care, liver cancer screening every 6 months if cirrhosis is present, joint treatment, hormone replacement.

Diet and lifestyle

• Avoid iron supplements and vitamin C supplements (which increase iron absorption).
• Limit alcohol, and avoid it entirely with liver damage.
• Do not eat raw shellfish, which can carry Vibrio vulnificus, a bacterium dangerous to people with iron overload.
• A normal balanced diet is fine; strict low-iron diets are usually unnecessary because phlebotomy is so effective.
• Get vaccinated against hepatitis A and B.

Outlook

People diagnosed and treated before cirrhosis or diabetes develop have a normal life expectancy. Fatigue, abdominal pain and skin darkening often improve with treatment; liver damage may partly reverse. Joint pain, cirrhosis and diabetes often do not reverse, which is why early detection and family screening matter.

Frequently asked questions

What are the first signs of hemochromatosis?

Early signs are often vague: tiredness, weakness, joint pain (especially in the knuckles of the index and middle fingers), abdominal discomfort and low sex drive. Many people have no symptoms and are diagnosed after a routine blood test shows high iron.

How is hemochromatosis diagnosed?

It is diagnosed with blood tests for transferrin saturation and ferritin, followed by HFE genetic testing. Liver tests, ultrasound, elastography or MRI assess organ damage. Relatives of someone with hemochromatosis should be tested.

How is hemochromatosis treated?

The main treatment is phlebotomy, removing blood regularly to reduce iron. It starts weekly until iron levels are normal, then continues every few months for life. Avoiding iron and vitamin C supplements and limiting alcohol also help.

Is hemochromatosis serious?

It can be if untreated, causing cirrhosis, liver cancer, diabetes, heart failure and arthritis. When diagnosed early and treated with regular phlebotomy, most people live normal, healthy lives.

Should I avoid red meat with hemochromatosis?

A strict low-iron diet is usually not needed because phlebotomy controls iron very effectively. It is reasonable to avoid iron-fortified foods and supplements, limit large amounts of red meat and alcohol, and never take vitamin C or iron supplements without advice.