Haemochromatosis is a condition in which the amount of total body iron is increased. The excess iron is deposited in and causes damage to several organs, including the liver. Hereditary haemochromatosis is the commonest cause of haemochromatosis and has autosomal recessive inheritance.
Hereditary haemochromatosis is the most common heritable genetic condition in Northern Europe. Most male patients are diagnosed at the age 40-50; females are usually diagnosed decades later due to menstrual iron loss.
Most cases of haemochromatosis are hereditary in nature.
Hereditary haemochromatosis (HHC)
Secondary (from iron overload)
Parenteral iron-loading e.g. repeated transfusions
Iron-loading anaemia e.g. thalassaemia, sideroblastic anaemia
90% of patients with HHC have a homozygous C282Y mutation in HFE protein. This leads to increased absorption of dietary iron. Iron is deposited throughout the body and total iron may reach 60-80 grams (compared to 4 grams in healthy individuals).
The organs most affected are:
- Pancreatic islets
- Endocrine glands
Iron metabolism in HHC
The pathological mechanism is unclear. It is thought that the defective HFE cannot interact with transferrin, leading to reduced uptake of transferrin-associated iron. Consequently, enterocyte iron transporters are upregulated to increase intestinal iron absorption.
In the liver, iron deposition first starts in periportal hepatocytes and later extends to all hepatocytes. Fibrous septa gradually develop, leading to irregular nodules. Subsequent regeneration produces cirrhosis.
Most patients are asymptomatic. Symptomatic patients are usually males above the age 40.
The classic symptoms of haemochromatosis are:
- Bronzed skin (leaden-grey skin pigmentation due to increased melanin)
- Diabetes mellitus
Other features include:
- Fatigue and malaise
- Heart failure
- Arthritis with chondrocalcinosis due to calcium pyrophosphate deposition
- Sexual symptoms – impotence, loss of libido, testicular atrophy
The most routinely used tests for haemochromatosis are bloods and genetic testing.
- Bloods may show:
- Raised ferritin
- Raised iron levels
- Raised transferrin saturation
- Saturated iron-binding capacity
- Genetic testing: Used routinely to identify mutations in C282Y and H63D
- Liver biopsy: can assess fibrosis and distribution of iron
- MRI liver: has good specificity but poor sensitivity for detecting iron overload
The management options for haemochromatosis include venesection, organ treatment and dietary adjustments.
Initial treatment involves weekly venesection of 500 mL blood (containing 250 mg iron) until serum iron is normal and ferritin levels <50 µg/L. This may take two years or more to achieve. Once iron and ferritin levels are well-controlled, venesection can be offered as required maintain normal ferritin levels.
Venesection can resolve liver and cardiac problems but will not resolve diabetes mellitus.
Treat cirrhosis, diabetes and heart failure symptomatically.
The intake of alcohol, vitamin C and red meat should be limited. Substances that inhibit calcium absorption should be encouraged, such as high tannin tea.
Family members of patient with HHC should be offered screening for the condition.
Pre-cirrhotic HHC has a normal life expectancy. Compared to other causes of cirrhosis, cirrhotic HHC has a good prognosis.
Hepatocellular carcinoma is an important cause of death in HHC.