Table 1

HH types	Phenotype MIM number	Gene MIM member	Location/ Gene Map Locus	Inheritance	Gene productfunction	Clinicalfeatures	Laboratoryfinfings	Liverpathology	Functionalconsequences of mutations
1	235200	HFE, (HLA-H) 613609	6p21.3	AR	Involved in hepcidin synthesis way BMP6, interaction with TFR1	Fatigue, lethargy, arthropathy, skin pigmentation, liver damage, diabetes mellitus,endocrine dysfunction, cardiomyopathy, hypogonadotropic, hypogonadism	serum ferritin transferrin saturation	Hepatocyte iron loading, fibrosis cirrhosis	Impaired hepcidin regulation by iron leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells
2A	602390	Hemojuvelin HJV, (HFE2) 608374	1p21	AR	Involved in hepcidin synthesis, BMP co-receptor	As for HFE Earlier onset (<30 yr). Cardiomyopathy and hypogonadism more prevalent	serum ferritin transferrin saturation	Hepatocyte iron loading, fibrosis, cirrhosis	Loss of hepcidin regulation, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells
2B	613313	Hepcidin HAMP, 606464	19q13	AR	Downregulation of iron efflux from enterocytes	As for HFE Earlier onset (<30 yr). Cardiomyopathy and hypogonadism more prevalent	serum ferritin transferrin saturation	Hepatocyte iron loading, fibrosis, cirrhosis	No/inactive hepcidin, leading to maximal iron absorption and release of iron from reticuloendothelial cells
3	604250	Transferrin Receptor 2 TFR2, 604720	7q22	AR	Involved in hepcidin synthesis, interaction with transferrin	As for HFE	serum ferritin Normal transferrin saturation	Hepatocyte iron loading, fibrosis, cirrhosis	Impaired hepcidin regulation by iron, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells
4	606069	Ferroportin SLC40A1, 604653 IREG1, MTP1	2q32	AD	Duodenal ironexport	Typical presentation: as for HFE, except generally milder. May have mild anemia and lower tolerance to phlebotomies	serum ferritin transferrin saturation	Predominant Kupffer cell iron loading, fibrosis	Reduced ferroportin iron transport ability, leading to accumulation of iron in reticuloendothelial cells
4	606069	Ferroportin SLC40A1, 604653 IREG1, MTP1	2q32	AD	Duodenal ironexport	Atypical: as for HFE	serum ferritin transferrin saturation	Predominant hepatocyte iron loading, fibrosis, cirrhosis	Loss of ferroportin regulation by hepcidin, leading to increased intestinal iron absorption and release of iron from reticuloendothelial cells

MIM: Mendelian Inheritance in Man; TFR1: transferring receptor 1, HFE: encodes HFE protein; HJV: encodes hemojuvelin; HAMP: encodes hepcidin; TFR2: encodes
transferring receptor 2; SLC40A1: encodes ferroportin; BMP6: bone morphogenetic protein 6; AR: Autosomal recessive; AD: autosomal dominant [2,4,16-19]

Table 1: Types of HH: genetic, clinical characteristics and laboratory features.