Hereditary hemochromatosis (HH) is an autosomal recessive inherited disorder of iron metabolism. Due to excessive intestinal absorption, iron accumulates in the parenchymal cells of the liver, pancreas, heart and other organs resulting in damage to its structure and its function impaired. It is one of the most common genetic diseases in Caucasians with a prevalence of about 1 in 300. Although the disease symptoms are often non-specific, much of the organ damage is irreversible once it has occurred. Early detection and treatment is therefore very important as part of preventive medicine.
A number of different HFE mutations have been described. Most HH cases (52-96%) in the European regions are associated with a homozygous mutation at position 845 (G –› A) of exon 4 of the HFE gene, which results in an amino acid change at position 282 from cysteine to tyrosine (C282Y). There is a second mutant allele at position 187 (C —› G), detected with a relatively high frequency in exon 2 of the HFE gene wherein the amino acid histidine is replaced by an aspartic acid at position 63 (H63D). The contribution of this allele for iron overload is most relevant in the case of heterozygosity combined with allele C282Y (C282Y/H63D). The third HFE mutation is a substitution at position 193 (A —› T) of exon 2 resulting in an amino acid change at position 65 from serine to cysteine (S65C) and has proven to be generally benign, although the C282Y / S65C genotype can impart a slight increase in disease risk, contributing to a mild disease phenotype. Many of the other HFE mutations described are private and rare, or found only in certain regions.
GENVINSET® HFE C282Y, GENVINSET® HFE S65C y GENVINSET® HFE H63D are kits for the determination of the C282Y, S65C and H63D mutations, associated with primary hemochromatosis, by Real Time PCR using TaqMan® probes technology.