266 - The laboratory diagnosis of hemochromatosis
Autor(s): P. Doretto
Issue: RIMeL - IJLaM, Vol. 6, N. 4, 2010 (MAF Servizi srl ed.)
Page(s): 266-73
Hemochromatosis is a clinical syndrome characterized by the toxic accumulation of iron in parenchymal cells of vital organs such as liver, heart and endocrine glands caused by mutations that affect genes that limit the iron entry into blood. The mutation of genes that codified proteins such as HFE, hepcidin, transferrin receptor 2, the hemojuvellina and ferroportin, has the effect of common pathogenetic hepcidin deficiency or resistance, common pathogenetic denominator in all forms of this syndrome. Hemochromatosis is usually associated to homozygosis for C282Y polymorphism in HFE, common in Caucasian populations, but only a minority has the full phenotypic expression of the disease, usually in association with abuse alcohol or other modifying factors. The diagnostic workup should not only identify the disease but to quantify the iron overload, define the stage of disease and identify risk factors for progression and early complications. The five successive steps include identification of the target population on which to run the investigation; evaluation for transferrin saturation and ferritin; if the transferrin saturation is >45%, perform genetic testing for C282Y and H63D mutations of HFE, in case of negativity, second-line genetic testing for rarer mutations; quantify iron overload by invasive (liver biopsy) or noninvasive assessments (ferritin, NMR SQUID); stages the phenotypic manifestations.