TABLE 6.
Hereditary systemic iron-overload disorders1
| Disorder | Inheritance | Laboratory markers | Clinical phenotype |
|---|---|---|---|
| HFE hemochromatosis (type 1) | Autosomal recessive | TSAT ↑ early | Primary hepatocyte iron loading, hepatic fibrosis/cirrhosis, liver cancer |
| SF ↑ | Cardiomyopathy | ||
| Diabetes mellitus | |||
| Hypogonadism | |||
| Arthropathy | |||
| Skin pigmentation | |||
| Juvenile HJV hemochromatosis (type 2A) | Autosomal recessive | TSAT ↑ early | Similar to HFE hemochromatosis, but early onset and accelerated course, endocrine and cardiac disease more prominent than hepatic involvement |
| Juvenile HAMP hemochromatosis (type 2B) | Autosomal recessive | SF ↑ | |
| TFR2 hemochromatosis (type 3) | Autosomal recessive | TSAT ↑ early | Similar to HFE hemochromatosis |
| SF ↑ | |||
| FPN1 loss of function (type 4A) | Autosomal dominant | SF ↑ | Predominant macrophage iron loading in the liver, spleen, and bone marrow |
| TSAT often normal | Later parenchymal iron accumulation with mild liver disease | ||
| May have mild anemia | |||
| FPN1 gain of function (Type 4B) | Autosomal dominant | TSAT ↑ early | Similar to HFE |
| SF ↑ |
1 FPN1, ferroportin 1; HAMP, gene encoding hepcidin; HFE, human hemochromatosis; HJV, hemojuvelin; SF, serum ferritin; TFR2, transferrin receptor 2; TSAT, percentage transferrin saturation; ↑, increase. Adapted with permission from reference 390.