Hemochromatosis, gentic

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Hereditary haemochromatosis is a genetic disease characterised by excessive accumulation of iron (Fe) in tissues, possibly leading to tissue damage.

The most common cause of hereditary haemochromatosis are point mutations (C282Y/H63D) in the HFE gene ("high Fe", Fe = iron) leading to a malfunctioning protein product. Subsequently, these distinct mutations in the HFE gene cause a disturbance in the iron hemostasis of the body as the HFE protein plays a crucial role in the process of iron sensing and absorption. In the beginning the resulting iron overload in the body can cause rather unspecific smyptoms (such as fatique, weakness or joint pain), but can sometimes lead to serious consequential damage (e.g. liver cirrhosis, hepatocellular carcinoma, thyroid problems, heart failure, erectile dysfunction) further down the road.

Diagnosis is made by testing for increased serum ferritin, iron and transferrin saturation and is confirmed by genetic testing.


- Homozygous C282Y mutation:
Most common genotype in clinically symptomatic haemochromatosis (approximately 90% of cases). The majority of people with this variant is, however, clinically unremarkable. If there is an iron overload and corresponding clinical symptoms, the findings indicate HFE-associated haemochromatosis. A bloodletting treatment should be started if the ferritin level exceeds the standard upper limit. Clinically normal people with homozygocity should have their iron levels tested regularly. An assessment of close relatives is indicated.

- Heterozygous C282Y mutation:
No indication of the most common form of haemochromatosis. Heterozygocity for C282Y may be accompanied by slightly raised iron levels. With extremely raised levels and/or clinical symptoms, an assessment to find other causes (metabolic syndrome, fatty liver, other rare genetic forms of the disease) is indicated.

- Homozygous H63D mutation:
No indication of the most common form of hereditary haemochromatosis. This genotype is rarely accompanied by slightly increased iron levels. With extremely raised levels and/or clinical symptoms, an assessment to find other causes (metabolic syndrome, fatty liver, other rare forms of the disease) is indicated.

- Heterozygous C282Y and heterozygous H63D mutation (compound heterozygous):
No indication of the most common form of hereditary haemochromatosis. This constellation (compound heterozygote) may be accompanied by slightly raised iron levels. With extremely raised levels and/or clinical symptoms, an assessment to find other causes (metabolic syndrome, fatty liver, other rare genetic forms of the disease) is indicated.