Vnitr Lek 2005, 51(9):995-1006

Disorders of iron metabolism. Part 2

J. Novotný

Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc., Transfuzní oddělení a krevní banka FN Brno, pracoviště Bohunice, přednosta prim. MUDr. Eva Tesařová

Disorders of iron metabolism are very frequently seen in clinical medicine. Up to 60% of women in gestational age suffer from some degree of sideropenia. Sideropenia occurs in situations with the negative bilance of this vital element - i.e. in patients with chronic blood loss, in vegetarians or in malaabsorptive syndromes and in states with increasing utilization of iron in gravidity, lactation or in pubescents. The iron overload represents the opposite situation and is found mainly in transfusion dependent patients, in some hemolytic states with inefective erythropoesis, in severe hepatopathias and in patients with congenitaly incerased absorption of iron - i.e. in hereditary hemochromatosis type I-V. The classical hereditary hemochromatosis (type I) was firstly described in the 19th century as so called "bronze diabetes". It was the full penetrance of hereditary iron overload which affected the parenchymatous organs (mainly the liver), heart, joints, skin and endocrine glands. The main candidate gene was firstly described in 1966 by Feder et al. and was called HFE gene. HFE gene maps to the 6th chromosome close to the HLA locuses and reveals with the MHC (main histocompatibility complex) genes some homology. Mature HFE protein is associated with β2microglobuline and localized in the cytoplasmatic membrane, where this complex associates with transferrin receptors. This interaction with the transferrin receptors modulates the endocytosis of transferrin iron; there is not consensus in the literature about sense of the modulation (potentiation or inhibition of transferrin iron endocytosis). More than 30 mutations and polymorphisms in the HFE gene were discovered; the most frequent are the point mutations C282Y, H63D, and S65C. The most frequent genetic basis of hereditary hemochromatosis in caucasoids is the C282Y mutation, prevalence of heterozygotes in the Caucasoid populations being from 5 to 12 percent. The C282Y mutation can be revealed in about 80% of Caucasoid patients with the diagnosis of hereditary hemochromatosis. The classic hereditary hemochromatosis represents the autosomal recessive trait with incomplete penetrance, which is estimated in the broad interval from 1 to 50 percent. The mutations in other genes, which code for other proteins of iron metabolism, were revealed. This mutations cause so called "non-HFE hemochromatoses". The clinical picture of these deseases may be other than the picture of classic hemochromatosis, some the non-HFE iron overloads may be inherited in the dominant manner. The most frequently disscussed topic today is the exact mechanism/s leading to iron overload in HFE and non-HFE hemochromatosis, the genetic screening for HFE mutations in general population at risk and the relation of iron overload to atherosclerosis, diabetes and malignant diseases. These and other problems are under intensive research in many centres and only the future will bring the answers to these important questions.

Keywords: iron; sideropenia; iron overload; hereditary hemochromatosis

Received: August 27, 2004; Accepted: October 26, 2004; Published: September 1, 2005  Show citation