Conditions · Metabolism: heme, bilirubin and iron
Hereditary hemochromatosis !
An inherited disease in which the gut absorbs too much iron, which deposits in the liver, pancreas, heart and joints.
Updated 2026-11-01
Structures involved
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In biochemistry
In physiology
Why it happens
- Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon
- Oxidative stress and free-radical injury
- Special stains in diagnosis: Congo red, Prussian blue, PAS, Ziehl–Neelsen, Gram
What it is
Primary iron overload from lack of hepcidin (or resistance to it), nearly always due to HFE C282Y homozygosity.
Who gets it
It is one of the most common genetic diseases in people of northern European descent. In Colombia and Latin America it is less frequent, but seen in people with European ancestry; secondary overload from transfusions is more common.
Causes
- Type 1: HFE (C282Y homozygous, or C282Y/H63D)
- Type 2 (juvenile): HJV or HAMP; type 3: TFR2; type 4: SLC40A1 (ferroportin)
Risk factors
- Male sex (women are protected by menstruation and pregnancy)
- Northern European ancestry
- Alcohol use
Pathophysiology
Low hepcidin leaves ferroportin always active: the duodenum absorbs too much iron and macrophages release it. Transferrin saturates and non-transferrin-bound iron appears, entering hepatocytes, pancreatic β cells, myocardium, pituitary and joints, where it generates free radicals and fibrosis.
Symptoms and signs
- Fatigue and joint pain, typically in the 2nd and 3rd metacarpophalangeal joints
- Bronze or greyish skin
- Diabetes («bronze diabetes»)
- Loss of libido and impotence
- Enlarged liver and abdominal discomfort
Diagnosis
- Clinical
- A man aged 40–60 or a postmenopausal woman with fatigue, joint pain, liver disease or diabetes, or an affected relative.
- Tests
- Transferrin saturation above 45 % and high ferritin; HFE genotyping; liver tests, glucose; liver biopsy only in doubtful cases or to stage fibrosis.
- Imaging
- MRI (T2*) to quantify iron in the liver and heart; elastography for fibrosis; echocardiography if there are cardiac symptoms.
Treatment
- Procedure
- Regular phlebotomy until ferritin normalises, then maintenance
- Medical
- Iron chelators (deferoxamine, deferasirox) when phlebotomy is not tolerated
- Lifestyle
- Avoiding iron and vitamin C supplements, alcohol and raw shellfish (Vibrio vulnificus)
- Follow-up
- Periodic liver ultrasound in cirrhosis to detect hepatocellular carcinoma
Complications
- Cirrhosis and hepatocellular carcinoma
- Diabetes
- Cardiomyopathy and arrhythmias
- Hypogonadism
- Arthropathy and chondrocalcinosis
Prognosis
If treated before cirrhosis, life expectancy is normal; the arthropathy may persist.
Prevention
- Screening first-degree relatives (saturation, ferritin and genotype)
Test yourself
Think of the answer, then tap the question to see it.
Which mutation causes most hereditary hemochromatosis?
Homozygous C282Y in the HFE gene.
Which hormone is lacking in hemochromatosis, and with what effect?
Hepcidin: without it ferroportin stays active and the gut absorbs too much iron.
What is the first lab test when hemochromatosis is suspected?
Transferrin saturation (above 45 %), together with ferritin.
Why do women present later?
They lose iron through menstruation and pregnancy until menopause.
Related conditions
- Porphyria cutanea tarda
- Thalassemias (α and β)
- Iron deficiency anaemia
- Cirrhosis
- Hepatocellular carcinoma
- Type 2 diabetes mellitus
- Heart failure
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Hereditary hemochromatosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); HFE gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Hemochromatosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); HAMP gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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