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Hemochromatosis - HFE

Clinical Features

Hereditary hemochromatosis is one of the most common genetically determined metabolic diseases. Increased iron absorption leads to iron overload of the organs as manifested by liver cirrhosis, hepatocellular carcinoma, cardiomyopathy, arthritis, skin pigmentation and diabetes mellitus ("bronze diabetes"). Endocrinological, neurological and psychiatric symptoms may occur. Due to pregnancy, menstruation and nursing, women are much less affected than men. The disease can be treated by repetitive venesections.

Genetic Information

Hereditary hemochromatosis is an autosomal recessive disease, i.e. there is a mutation in both parental genes on chromosome 6 (6p21.3). The most common pathogenic mutation is the C282Y mutation in the HFE gene causing an amino acid change from cysteine to tyrosine at amino acid position 282. 80 to 90 % of the affected individuals are homozygous for the C282Y mutation. 4-8% of the patients carry different mutations on each of the alleles (compound-heterozygosity for the C282Y and H63D or S65C or Q283P mutations). In around 1% of the affected individuals only the C282Y mutation can be identified, whilst the second mutation is a very rare or yet unknown mutation. Homozygous mutation carriers are at increased risk for the clinical manifestation of hemochromatosis. In these individuals, serum ferritin and transferrin saturation should be screened regularly.

Prevalence

1 : 400 in the Middle-European population
Carrier frequency: approximately 1 : 10

Diagnostic