Analysis index

1 ml EDTA blood

Increased ferritin levels and/or increased transferrin saturation, unclear GOT- and/or GPT elevation. Liver cirrhosis of unknown origin. Cardiomyopathy. Unclear arthropathies

PCR detection of the C282Y- and H63D-mutation in the HFE gene

Early detection of hemochromatosis is important to enable early treatment in order to prevent irreversible organ damage. Age needs to be considered when assessing the ferritin- and transferrin saturation values, as in case of hemochromatosis the iron storage increases with age. Thus in a 30-year-old, slightly increased ferritin- and transferrin saturation levels may already be an indication for a hereditary hemochromatosis. The hereditary hemochromatosis is the most common autosomal-recessive hereditary disease. There is no manifest disease in heterozygous genetic HFE-gene mutation carriers; however, a heterozygous trait may cause a moderate iron accumulation and may have a disadvantageous influence towards a concomitant liver disease (caused by alcohol, hepatitis C and others). A homozygous HFE gene mutation is found in approximately 82 % of patients with hereditary hemochromatosis (Healthy persons: 0,0 – 0,5 %, heterozygous frequency in the total population 3,9 %), however there is reduced penetrance even in case of homozygotism, only a part of the affected persons develop manifest disease (men more often than women). Regular monitoring of the iron balance (transferrin saturation) is indicated. H63D is a further predisposing mutation in the HFE gene for iron overload with very low penetrance. It is often apparent in the normal population (heterozygous frequency 15 %). In persons with suspicion of hereditary hemochromatosis, quite often there is a combination of heterozygous C282Y mutation and heterozygous H63D mutation, the so-called compound-heterozygotism (4,5 %), although the phenotypical penetrance is very low (1 – 2 %).

Further rare reasons for hemochromatosis are mutations in the hemojuvelin gene (hemochromatosis type II, autosomal-recessive inheritance), mutations in the TFR2 gene (transferrin receptor II, hemochromatosis type III, autosomal-recessive inheritance) and mutations in the SLC40A1 gene (ferroportin I, hemochromatosis type IV, autosomal-dominant inheritance).