TABLE 1.
Human HH type (mutant gene) | Mouse model | Mouse phenotype | Human phenotype | References |
---|---|---|---|---|
Type 1 (HFE) | Hfe −/− Hfe C282Y/C282Y Hfe C282Y/H63D | Decreased hepcidin, elevated TSAT, increased body iron (liver), increased intestinal Fe absorption, cardiac hypertrophy; no hepatic fibrosis or cirrhosis | Adult-onset; liver disease usually predominates, but endocrine disorders, cardiac problems, and joint disease also occur | (55–58) |
Type 2A (HJV) | Hjv −/− | Decreased hepcidin, elevated TSAT, increased body iron (liver, pancreas, heart), splenic iron sparing; do not develop diabetes or cardiomyopathy | Juvenile-onset; cardiomyopathy and endocrinopathies predominate; parenchymal iron accumulation in liver | (59, 60) |
Type 2B (HAMP) | Hamp1 −/− | No hepcidin, increased body iron (liver, pancreas, heart), splenic iron sparing, centrolobular accumulation of liver iron | Juvenile-onset; similar to Type 2A | (61, 62) |
Type 3 (TFR2) | Tfr2 −/− | Decreased hepcidin, elevated TSAT, increased hepatic iron, splenic iron sparing | Adult-onset; similar to Type 1 | (63, 64) |
Type 4 (SLC40A1; encoding FPN1) | Fpn ffe | Iron loading in hepatic Kupffer cells, high serum ferritin, low TSAT | “Ferroportin disease”; macrophage iron trapping, low TSAT, anemia | (65) |
ffe, Flatiron; FPN, ferroportin 1; HAMP, hepcidin antimicrobial peptide gene; HFE, homeostatic iron regulator; HH, hereditary hemochromatosis; HJV, hemojuvelin; SLC, solute carrier; TFR, transferrin receptor; TSAT, transferrin saturation.