What's hereditary hemochromatosis?
Hereditary hemochromatosis is an inherited disorder of iron metabolism in which the body takes in and stores too much iron over time. The most common form is autosomal recessive and linked to the HFE gene, chiefly the C282Y change, with H63D a second, less penetrant variant.
| Also indexed as | OMIM:235200, MONDO:0021001 |
|---|---|
| Features mapped | 16 |
| Treatments mapped | 1 |
| Published sources | 13 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Hepatocellular carcinoma
When iron builds up in the liver over many years it can cause scarring and, in some people, liver cancer.
Increased circulating ferritin concentration
Blood tests usually show a high ferritin level and high transferrin saturation; these are the markers used, alongside genetic and imaging tests, to identify the condition.
Elevated circulating iron concentration
The body absorbs too much iron from food because levels of the iron-regulating hormone hepcidin are too low.
Elevated circulating hepatic transaminase concentration
Iron building up in the liver can show up on blood tests as raised liver enzymes (aminotransferases), one of the typical signs of the condition.
Diabetes mellitus
Iron deposits in the pancreas can lead to diabetes, sometimes together with liver disease and a bronze colouring of the skin.
Impotence
People who build up too much iron may notice a range of symptoms, which can include a lower sex drive alongside joint discomfort, tiredness, and belly pain.
Cardiomyopathy
Iron can also affect the heart muscle, contributing to heart-muscle disease in a smaller number of people.
Arrhythmia
Iron in the heart can cause abnormal heart rhythms or heart failure.
Congestive heart failure
Long-standing iron overload can contribute to congestive heart failure, alongside fatigue, joint pain and diabetes.
Autosomal recessive inheritance
Inheriting the at-risk genotype does not by itself lead to disease; many people who have it never develop iron overload. Clinical penetrance is highly variable and can be very low: in large population screening, up to half of women and a fifth of men with two C282Y copies showed no iron-overload disease at all.
Hepatomegaly
The extra iron tends to collect in the liver, along with the heart, hormone-producing glands, and joints.
Cirrhosis
Iron overload can scar the liver (cirrhosis), which in turn raises the risk of liver cancer.
Abdominal pain
People who do develop iron overload may notice joint aches, fatigue, reduced sex drive and abdominal pain.
Hypogonadotropic hypogonadism
Iron can collect in the gonads, the glands that make sex hormones, which is one of the organs that can be affected as iron builds up across the body.
Arthropathy
Joint disease is often the symptom that most affects daily life and can be disabling.
Hyperpigmentation of the skin
Iron can collect in the skin as well as in organs such as the liver, heart, pancreas, and the glands that make sex hormones, and this build-up across several systems can cause damage over time.
How it is diagnosed
Hemochromatosis, type 1
Diagnosed using: HFE genetic testing.
“The diagnosis of HH is established by genetic testing in patients with elevated transferrin saturation values.”
Hemochromatosis, type 1
Diagnosed using: Transferrin saturation and serum ferritin.
“Suspicion of the disorder begins with personal and family history, transferrin saturation, and ferritin levels, and if high, genotyping to confirm the disorder.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
therapeutic phlebotomy
The main treatment is therapeutic phlebotomy, a recurring procedure that removes blood (and the iron it contains) on a schedule guided by ferritin and transferrin saturation. Started early, it can restore a normal life expectancy.
Used to help with: Hemochromatosis, type 1.
“Treatment with phlebotomy remains the first-line therapy, and if instigated early leads to a normal life expectancy.”
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
incomplete penetrance
Penetrance is incomplete and highly variable. Most people who carry the at-risk genotype, especially women, never develop iron-overload disease; the genotype raises risk but does not determine the outcome.
Described as modulating: Hemochromatosis, type 1.
“Genotype screening in large population studies has shown that the clinical penetrance of C282Y homozygosity is highly variable and can be very low, with up to 50% of women and 20% of men showing a silent phenotype.”
HFE C282Y homozygosity
The most common form comes from carrying two copies of the HFE C282Y change. It is common in people of Northern European descent (about 1 in 200), but most people who carry it, especially women, never develop iron-overload disease.
Described as modulating: Hemochromatosis, type 1.
“The most common form is HFE-hemochromatosis (HFE-H) due to p.Cys282Tyr (C282Y) homozygosity, present in nearly 1 in 200 people of Northern European descent but characterized by low penetrance, particularly in females.”
How to read the evidence labels
Where this comes from
This guide is built from 13 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.