Clinical aspects of hemochromatosis

Hemochromatosis is one of the most frequent genetic diseases among the whit e populations, affecting one in three hundred persons. Its diagnosis has be en radically transformed by the discovery of the HFE gene. In a given indiv idual, the diagnosis can, from now on, be ascertained on the sole associati on of a plasma transferrin saturation (TS) over 45% and homozygosity for th e C282Y mutation. Liver biopsy is only required to search for cirrhosis whe never there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevat ed serum AST. Family screening is mandatory, primarily centered on the sibl ings. The treatment remains based on venesection therapy which improves man y features of the disease (one of the most refractory, however, being the j oint signs) and permits normal life expectancy provided the diagnosis is es tablished prior to the development of cirrhosis or of insulin-dependent dia betes. In view of the prevalence, the non-invasive diagnosis, the spontaneo us severity and the efficacy of a very simple therapy, hemochromatosis shou ld benefit from population screening. This screening could be based, first, on the assessment of transferrin saturation, followed - when elevated - by the search for the C282Y mutation. The discovery of the HFE gene has also paved the road for the individualization of other types of iron overload sy ndromes which are not HFE-related. (C) 2000 Elsevier Science Ltd. All right s reserved.