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Hereditary Haemochromatosis is also occasionally called Bronze Diabetes or Siderophilia. The disease is a disorder of Iron handling, resulting in toxic accumulation of Iron within organs.

  • Haemochromatosis is the commonest autosomal recessive disease.
    • It is also the commonest inherited liver disease in whites.
  • Organs affected include the liver, heart, pancreas, adrenal glands, pituitary gland, skin and joints
  • Haemochromatosis is usually an adult-onset disease.
  • Humans are unable to excrete excess iron and usually balance absorption carefully against natural losses.

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  • Incidence = 1 in 300 [Carriers estimated at 1:10]
  • Age: presents in 5th decade (men) and 6th decade (women)
  • Sex - men:women 1.8:1
  • Ethnicity: Mostly people of northern european descent and particularly of Celtic origin.


HFE Gene - mutated in most patients with hereditary haemochromatosis.

  • Chromosome 6
  • HFE C282Y mutation ~ 90% of people with typical Haemochromatosis.
    • This is a missense mutation involving substitution of cysteine for tyrosine at position 282 of the HFE gene.
  • HFE interacts to reduce the affinity of transferrin receptors to transferrin, which is thought to modulate cellular iron uptake. It may also reduce ferritin levels.
  • Where the HFE gene is abnormal, ferritin levels are not under normal feedback control, leading to accumulation of iron in peripheral tissues.

Humans are unable to excrete excess iron. As such, we normally regulate our absorption of dietary iron closely against natural losses to maintain a balance.

  • Adult males lose 1mg of Iron daily, mainly from gastrointestinal and skin epithelial losses.
  • Females lose an average of an addition 1mg daily via menstrual losses
    • Pregnancy results in a 500mg loss
  • There is minimal loss of Iron in urine.

In haemochromatosis, dietary Iron absorption continues in the face of elevated total body iron levels.

  • Excess iron causes free radical formation which results in cell damage and fibrosis.

Clinical features

Most patients are asymptomatic at diagnosis, but were found to have elevated Iron levels on testing, or were screened due to an affected relative.

Symptoms and Signs include:

  • Severe fatigue
  • Liver disease
    • Hepatomegaly may be present initially
    • Cirrhosis occurs due to progressive Iron deposition
      • Investigate for portosystemic varices and risk of GI bleeding
      • Hepatocellular carcinoma may occur.
  • Skin pigmentation due to Iron deposition and melanin.
  • Arthropathy due to Iron accumulation within joints
    • Imaging: square bone ends with hook-shaped osteophytes, particularly within the MCP joints.
  • Diabetes mellitus due to Iron deposition in the pancreas.
  • Impotence in males due to hypogonadism due to pituitary damage from Iron accumulation.
  • Cardiomyopathy (usually dilated) due to myocardial damage from Iron accumulation
    • May be the presenting complaint (~15%)
    • May present with arrhythmias or congestive cardiac failure


  • Serum Transferrin Saturation
    • Persistently elevated in the absence of other causes of Iron overload.
    • Screening threshold = 45-50% fasting transferrin saturation
      • young women with haemochromatosis may not have an elevated transferrin saturation
  • Serum Ferritin
  • Liver biopsy - high iron concentration / staining
    • also allows assessment of stage of liver disease
    • No longer essential for diagnosis if genetic test +ve.
  • HFE Gene testing
    • Recommended for all 1st degree relatives of an affected patient.
    • Recommended where there is evidence of iron overload (first three tests)


Early diagnosis and treatment before cirrhosis occurs allows a normal lifespan.

Treatment is via venesection

  • Weekly 500ml whole blood (200mg Iron)
    • Continue until Haemoglobin fails to recover before the next venesection and until
    • Transferring saturation <50%
  • Maintenance phlebotomy: 1 unit of blood every 2-3 months.


  • Alcohol should be avoided; it also increases iron absorption.
    • Red wine contains high levels of iron
  • Iron supplements should be avoided
  • Consumption of red meats and organs should be restricted.
  • Shellfish can cause sepsis in patients with haemochromatosis - cook thoroughly.

Liver Transplantation is the only therapeutic option for end-stage liver disease.

Orthopaedic surgery may be necessary for severe arthropathy.

Other complications requiring management include:

  • Gastroesophageal bleeding
  • Hepatic encephalopathy
  • Sepsis
  • Congestive heart failure
  • Arrhythmias
  • Hepatocellular carcinoma
  • Diabetes mellitus
  • Hypogonadism
  • Arthropathy
  • Thyroid dysfunction


Screening for Hepatocellular Carcinoma

  • Regular Alpha foetoprotein (AFP) and ultrasound scanning


Prognosis depends on early diagnosis and the absence of hepatic damage.

  • Early diagnosis and venesection can prevent all complications and allow a normal life span.
  • Morbidity and mortality correlates with stage of liver disease.


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