Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation.

Epidemiology

• 1 in 10 people of European descent carry a mutation in the genes affecting iron metabolism, mainly HFE
• prevalence in people of European descent = 1 in 200, making it more common than cystic fibrosis

Aetiology

• It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6
• There are rare cases of families with classical features of genetic haemchromatosis but no gene mutations

Pathophysiology

• In patients with haemochromatosis, mutations in the genes HFE, HJV and TfR2 interrupt hepcidin synthesis.
• Therefore, in the intestinal cells, a deficiency of hepcidin leads to less ferroportin being bound and thus more iron will be released into the plasma.

PC

It is often asymptomatic in early disease

• early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
• 'bronze' skin pigmentation
• diabetes mellitus and diabetes insipidus
• liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)