RESUMO
HFE hemochromatosis is the most frequent genetic iron overload disease. It is linked to the C282Y mutation of the HFE protein, protein encoded by the HFE gene, which is located on chromosome 6. The mechanisms accounting for iron excess are not only digestive hyperabsorption of iron but also excessive recycling of macrophagic iron coming from erythrophagocytosis and secreted into the blood. Both mechanisms are linked to an HFE-related hepatic failure in producing hepcidin, a key hormone of body iron regulation. The marked phenotypic variability of C282Y homozygosity expression is likely related to both genetic and environmental factors. The HFE gene discovery has rendered non invasive the positive diagnostic of HFE hemochromatosis, which is now based first on an increased level of plasma transferrin saturation leading to the request of the HFE mutation. Then, hepatic MRI is a reliable method to quantify iron overload. The HFE gene discovery has also paved the road of an enlarged field of differential diagnoses corresponding to novel entities of non-HFE related genetic iron overload syndromes.
Assuntos
Hemocromatose/diagnóstico , Hemocromatose/etiologia , Antígenos de Histocompatibilidade Classe I/fisiologia , Proteínas de Membrana/fisiologia , Substituição de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/deficiência , Peptídeos Catiônicos Antimicrobianos/fisiologia , Cromossomos Humanos Par 6/genética , Análise Mutacional de DNA , Diagnóstico Diferencial , Duodeno/metabolismo , Regulação da Expressão Gênica , Hemocromatose/genética , Proteína da Hemocromatose , Hepatócitos/metabolismo , Hepcidinas , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Absorção Intestinal , Ferro/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto , Fagocitose , Fenótipo , Mutação Puntual , Transferrina/análiseRESUMO
Hereditary Hemochromatosis is an autosomal recessive disease, characterized by chronic iron overload. It is mainly due to mutations of the HFE-1 gene. In the large majority of patients, the substitution of tyrosine for cysteine at amino acid 282 (C282Y) is found at the homozygous state. Since the HFE-1 hemochromatosis identification, several other entities of iron overload have been individualized. In the present article, the frequency, penetrance and pathophysiology of HFE-1 hemochromatosis as well as various clinical presentations resulting from different mutations affecting different proteins involved in iron metabolism are described.