Type 1 is classic hereditary hemochromatosis, also termed HFE-related hemochromatosis. More than 80% of cases are caused by the homozygous C282Y mutation or the C282Y/H63D compound heterozygote mutation. Homozygous H63D mutations occur rarely and have the same phenotype as homozygous C282y cases. The disorder is autosomal recessive, with a homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in people of northern European ancestry. The C282Y and H63D mutations are uncommon among people with African ancestry and rare among people with Asian ancestry. Of patients with clinical features of hemochromatosis, 83% are homozygous. However, for unknown reasons, phenotypic (clinical) disease is much less common than predicted by the frequency of the gene (ie, many homozygous people do not manifest the disorder).

Type 2 hereditary hemochromatosis (juvenile hemochromatosis) is a rare autosomal recessive disorder caused by mutations in the HJV gene that affect the transcription protein hemojuvelin, or mutations in the HAMP gene, which directly codes for hepcidin. It often manifests in adolescents.

Mutations in transferrin receptor 2 (TFR2) gene that codes for a protein that appears to control saturation of transferrin, can cause a rare autosomal recessive form of hemochromatosis.

Type 4 hereditary hemochromatosis (ferroportin disease) occurs largely in people of southern European ancestry. It results from an autosomal dominant mutation in the SLC40A1 gene and affects the ability of ferroportin to bind hepcidin.

In transferrin deficiency (hypotransferrinemia or atransferrinemia), absorbed iron that enters the portal system not bound to transferrin is deposited in the liver. Subsequent iron transfer to sites of red blood cell production is reduced because of transferrin deficiency.

In ceruloplasmin deficiency (aceruloplasminemia), lack of ferroxidase causes defective conversion of Fe2+ to Fe3+; such conversion is necessary for binding to transferrin. Defective transferrin binding impairs the movement of iron from intracellular stores to plasma transport, resulting in accumulation of iron in tissues.