Other Forms of Hemochromatosis

Less Common Forms ofHemochromatosis

Mutations in other genes involved in iron metabolism have been identified, and these are responsible for other inherited forms of hemochromatosis. They are much less common than HFE hemochromatosis.

Juvenile Hemochromatosis

Juvenile Hemochromatosis (JH, also known as Type IIa and IIb Hemochromatosis) affects children and young adults, and is much more severe than Type I HFE hemochromatosis. Excess iron absorption and resulting iron overload occurs much earlier in JH, causing significant endocrine, cardiac and liver problems before age 30. The excess iron seems to particularly affect the heart in these young patients who often die of heart failure in their twenties if undiagnosed. Mutations in two different genes cause JH: the hemojuvelin gene on chromosome 1, and the hepcidin gene on chromosome 19. JH is inherited in an autosomal recessive pattern, and has been detected in a large variety of ethnic populations.

Hemochromatosis Type III

Hemochromatosis Type III is caused by mutations in a gene called Transferrin Receptor 2 (TFR2) on chromosome 7. The clinical symptoms are similar to the classic HFE-HHC, but typically occur earlier in age (30-50 years) than the HFE-HHC. TFR2-hemochromatosis is now considered to be an intermediate iron overload disorder, in between the adult onset HFE-HHC and Juvenile Hemochromatosis. It is also autosomal recessive and is much more rare than the classic HFE-HHC, found in only Southern European and Japanese populations so far.

Ferroportin Disease (Type IV Hemochromatosis)

Ferroportin disease (Type IV Hemochromatosis) is also an adult onset condition, caused by mutations in a gene called ferroportin on chromosome 2. This form of hemochromatosis is inherited in an autosomal dominant pattern which means that a person only needs one copy of the gene to develop the disease. This condition also has a different profile from other forms of hemochromatosis. Ferroportin disease causes high levels of ferritin with near normal levels of transferrin saturation, resulting in only minor organ damage. Individuals only rarely develop significant disease, but the condition may cause other health problems, and so it is treated differently than other forms of hemochromatosis.

Neonatal Hemochromatosis

Neonatal hemochromatosis is an iron storage disorder in which excess iron buildup in the liver is the result of infectious, inflammatory, immunological and possibly genetic factors. It typically presents during pregnancy and up to a few weeks after birth. Survival is only 30 per cent, despite aggressive medical therapy and even liver transplantation. The recurrence risk for future pregnancies by the same parents can unfortunately be as high as 80%.

Secondary Hemochromatosis

To make iron overload even more confusing, some forms are clearly not inherited but are as a result of other diseases, and therefore called secondary hemochromatosis. Iron overload can occur from multiple blood transfusions, a requirement for such disorders as chronic leukemia and thalassemias. In hemolytic anemia, a heterogeneous group of disorders, there is excess breakdown of red blood cells with subsequent spillage of iron into the bloodstream, and eventually the organs. The outcome is exactly the same as Type I Hemochromatosis but the treatment is different. Rarely, secondary hemochromatosis may occur from excessive ingestion of iron.