Epidemiology

There are four main types of haemochromatosis.[4][7]​​ The most common form, type 1, is caused by mutations in the HFE gene (haemostatic iron regulator) and occurs primarily in people of northern European descent.[2][3]​​[4][7]​​[8]​​​​​​[9]​​ While precise estimates vary, the prevalence of HFE-related haemochromatosis is similar in the US, Europe, and Australia, at approximately 1 case per 200 to 400 people.[4][7][10]​ The major HFE mutation (C282Y) is common in the US: 1 in 10 white people is heterozygous for this mutation, while approximately 1 in 200 is a C282Y homozygote.[3][11]​ The frequency of C282Y homozygosity is much lower in other ethnicities including Hispanic people (0.27 per 1000), Pacific Islanders (0.12 per 1000), and black people (0.14 per 1000).[3][11]​​ The homozygous C282Y mutation is present in approximately 80% to 90% of patients of northern European origin who have type 1 haemochromatosis.[2][8]​ Globally, the frequency of this mutation may vary and other genetic mutations may predominate.[12][13][14][15][16][17][18][19][20][21]​​​​ For example, in Ecuador the frequency of C282Y was reported as 0%.[16]​

The rarer forms of haemochromatosis (types 2-4), involving mutations in other genes, have been reported worldwide.

Although type 1 haemochromatosis is an autosomal-recessive condition, with approximately equal numbers of male and female homozygotes, it shows heterogeneous clinical expression, which is more common in men.[9]​ Iron loss through menses and pregnancy is thought to attenuate disease manifestations in female homozygotes, although other factors may also be involved.[22]​​ One large study of patients of northern European descent (aged 40-69 years) showed that among C282Y homozygotes, iron overload-related disease was seen in 28% of men and 1.2% of women.[23]

The risk of clinical disease increases with age.[8][24] In classic haemochromatosis, symptoms become clinically apparent in the fourth or fifth decade of life.​

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