The classification of hereditary abnormalities of iron metabolism was recently 
expanded and diversified. Genetic hemochromatosis now corresponds to six 
diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2 
due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3 
due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4 
caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6 
whose gene is hepcidine (HAMP). Systemic iron overload is also associated with 
aceruloplasminemia, atransferrinemia and the "Gracile" syndrome caused by 
mutations in BCS1L. The genes responsible for neonatal and African forms of iron 
overload are unknown. Other genetic diseases are due to localized iron overload: 
Friedreich's ataxia results from the expansion of triple nucleotide repeats 
within the frataxin (FRDA) gene; two forms of X-linked sideroblastic anemia are 
due to mutations within the delta aminolevulinate synthetase (ALAS 2) or ABC-7 
genes; Hallervorden-Spatz syndrome is caused by a pantothenate kinase 2 gene 
(PANK-2) defect; neuroferritinopathies; and hyperferritinemia--cataract syndrome 
due to a mutation within the L-ferritin gene. In addition to this wide range of 
genetic abnormalities, two other features characterize these iron disorders: 1) 
most are transmitted by an autosomal recessive mechanism, but some, including 
hemochromatosis type 4, have dominant transmission; and 2) most correspond to 
cytosolic iron accumulation while some, like Friedreich's ataxia, are disorders 
of mitochondrial metabolism.