Hereditary
hemochromatosis is an inherited autosomal recessive disease, associated to a mutation in the recently described HFE gene, which is located on the short arm of chromosome 6. The product of this gene combines with the beta-2-microglobulin and the
ferritin receptor, and regulates the
iron absorption in the small intestine crypt cells. It is possible that the mutation may cause the increased
iron uptake by the intestinal cells. The disease is very much common in men after the forties, and its expression is influenced by concomitant
alcoholism,
iron rich diet, oral and parenteral
iron administration, menstrual blood loss or abnormal
hemorrhages, blood donations, pregnancy, lactation, and
iron malabsorption clinical conditions, like
celiac disease. Many patients are asymptomatic, and the diagnosis may be suspected by
hepatomegaly of unknown cause, abnormal
iron metabolism tests, increased serum
aminotransferase levels,
diabetes mellitus, and anonymous
arthropathy. Less commonly hereditary
hemochromatosis presented by symptoms and signs of chronic
liver disease, or by the classic triad described by Trousseau skin pigmentation,
hepatomegaly and
diabetes mellitus. The diagnosis is confirmed by the increased serum
ferritin levels and
transferrin saturation, and the stainable
iron in hepatocytes, measured by scale devised by Scheuer et al, or the measurement of the hepatic
iron. The C282Y mutation was found in 64 to 100% of patients; eventually, subjects with hepatic
iron overload identical to hereditary
hemochromatosis has no mutation, and homozygous for the C282Y mutation do not express
iron overload.
Iron is best and quickly removed by weekly or twice-weekly phlebotomy of 500 ml, containing approximately 250 mg
iron. One to 3 years of weekly phlebotomy may be required to reduce stores to normal. As a guide to long-term maintenance
therapy, is recommended phlebotomy every 3 months and the serum
ferritin level should be maintained by less than 50 ng/ml.