Emocromatosi ereditaria: Dalla genetica alla clinica

Hereditary hemochromatosis is one of the most common autosomal recessive disorder among Caucasians since the genotype at risk for hemochromatosis accounts for 1:200-400 individuals of Northern European ancestry. The disease is characterized by an inappropriately increased intestinal iron absorption leading to early abnormalities of iron parameters followed by iron deposition in different organs. Excessive iron causes tissue damage and fibrosis, leading to organ failure. Clinical complications appear late in life and include liver cirrhosis, diabetes, cardiomyopathy, hypogonadism, arthropathy, skin pigmentation and susceptibility to liver cancer. Clinical symptoms develop only in homozygotes. Heterozy-gotes may show abnormalities of iron parameters, but are not clinically affected, unless carriers of other conditions which modify iron metabolism, such as chronic liver diseases, beta-thalassemia trait or other haemolytic anemias. The phenotypic expression of the disease is variable even within the same family, due to the effect of modifier genes or to environmental factors. Recent progress of genetics and molecular biology have shown that hemochromatosis is an heterogeneous disease, that may result from the inactivation of different genes. The identification of mutations of HFE and of other genes involved in the disease has allowed to develop molecular tests to support early diagnosis, allowing also to ameliorate the differential diagnosis with other iron loading disorders. In addition, the increased knowledge acquired from the study of hemochromatosis has contributed to clarify the pathophysiology of iron metabolism. For this reason hemochromatosis is considered a typical example of molecular medicine.