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Copyright ©2007 Baishideng Publishing Group Co.
World J Gastroenterol. Sep 21, 2007; 13(35): 4690-4698
Published online Sep 21, 2007. doi: 10.3748/wjg.v13.i35.4690
Table 1 Genetic, clinical and laboratory features of the various types of Hereditary Haemochromatosis
HHTypeGeneInheritanceClinical featuresLaboratoryfindingsLiver pathologyFunctional consequences ofmutations
1HFEAutosomal recessiveMay include: fatigue, lethargy, arthropathy, skin pigmentation, liver damage, diabetes mellitus, endocrine dysfunction, cardiomyopathy, hypogonadotropic hypogonadism↑ serum ferritin, ↑ transferrin saturationHepatocyte iron loading, fibrosis, cirrhosisImpaired hepcidin regulation by iron, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells
2AHemojuvelin(HJV)Autosomal recessiveAs for HFE. Earlier onset (< 30 yr). Cardiomyopathy and hypogonadism more prevalent.↑ serum ferritin, ↑ transferrin saturationHepatocyte iron loading, fibrosis, cirrhosisLoss of hepcidin regulation, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells
2BHepcidin(HAMP)Autosomal recessiveAs for HFE. Earlier onset (< 30 yr). Cardiomyopathy and hypogonadism more prevalent.↑ serum ferritin, ↑ transferrin saturationHepatocyte iron loading, fibrosis, cirrhosisNo/inactive hepcidin, leading to maximal iron absorption and release of iron from reticuloendothelial cells
3TransferrinReceptor 2(TfR2)Autosomal recessiveAs for HFE.↑ serum ferritin, ↑ transferrin saturationHepatocyte iron loading, fibrosis, cirrhosisImpaired hepcidin regulation by iron, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells
4Ferroportin(Fpn), SLC40A1, IREG1, MTP1Autosomal dominantTypical presentation: as for HFE, except generally milder. May have mild anaemia and lower tolerance to venesection.↑↑ serum ferritin, normal transferrin saturationPredominant Kupffer cell iron loading, fibrosisReduced ferroportin iron transport ability, leading to accumulation of iron in reticuloendothelial cells
Atypical: as for HFE↑ serum ferritin, ↑ transferrin saturationPredominant hepatocyte iron loading, fibrosis, cirrhosisLoss of ferroportin regulation by hepcidin, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells