Hemochromatosis, Type 5

A number sign (#) is used with this entry because of evidence that hemochromatosis type 5 is caused by heterozygous mutation in the FTH1 gene (134770) on chromosome 11q12. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200.

Clinical Features

Kato et al. (2001) studied a Japanese family segregating autosomal dominant iron overload. The proband was a 56-year-old woman who, during evaluation for early gastric cancer, was found to have low signal intensity of liver, heart, and bone marrow on MRI, indicative of iron deposition. Blood examination showed high serum ferritin level of 1,654 mcg/L, as well as an increase in both serum iron and transferrin saturation. Hematologic evaluation revealed no abnormalities. Liver biopsy showed heavy iron deposition in most hepatocytes and in some Kupffer cells, suggesting hemochromatosis. Examination of 7 more family members revealed that a sister and brother of the proband also had elevated serum ferritin levels, and abdominal MRI in the brother showed low signal intensity of the liver and bone marrow, consistent with iron deposition.

Molecular Genetics

In 3 affected members of a Japanese family segregating autosomal dominant hemochromatosis, who were negative for hemochromatosis-associated mutations in the HFE (613609) and TFR2 (604720) genes, Kato et al. (2001) identified a heterozygous mutation in the FTH1 gene (134770.0001). The mutation, which was not found in 42 unrelated controls, was also present in the proband's 28-year-old daughter, who had an apparently normal serum ferritin level. However, the authors noted because the daughter had just given birth and was breastfeeding, she was likely to exhibit an increased level of physiologic iron loss.