Hereditary haemochromatosis(HH) is an autosomal recessive-inheritable iron metabolism disorder, in which, despite sufficient iron stores, there is an inappropriately high absorption of iron. This leads to an excess of iron in the body and the deposition of iron in various organs, primarily in the liver.
The disease usually manifests itself in the middle-aged adult with increasedsk in pigmentation, diabetes mellitus,cirrhosis of the liver and cardiomyopathy.
In most cases (90%) the HFE gene contains a C282Y variant (p. C282Y) in a homozygous form. With clinical haemochromatosis, evidence of this variant confirms the diagnosisof an HH. Treatment with bloodletting and widening the genetic investigation to close relatives is indicated.
Homozygosity for C282Y alone without the occurrence of clinical features is, however, not sufficient for diagnosis because only 15-25% of the carriers of this variant develop the disease.
In asymptomatic carriers, a regular review of the iron levels is also recommended
in addition to the family assessment.
Moreover, with 5-10% of confirmed haemochromatosis sufferers, homozygosity cannot be proven.
Checks for other causes and genetic factors should be carried out in such patients.
This genetic investigation also tests for the H63D variant (p. H63D) which is relatively common in the population, because a compound heterozygosity of variants C282Y and H63D can accompany slightly elevated iron levels.
However, this compound heterozygosity is not considered a trigger for HH.