From the Guidelines
Hereditary hemochromatosis (HH) is primarily classified into HFE-related and non-HFE-related types, with the most common forms being HFE-related, including C282Y/C282Y and C282Y/H63D genotypes, as well as non-HFE-related types such as hemojuvelin (HJV), transferrin receptor-2 (TfR2), ferroportin (SLC40A1), and hepcidin (HAMP) mutations 1. The classification of hereditary hemochromatosis can be broken down into several key categories, including:
- HFE-related hemochromatosis, which includes genotypes such as C282Y/C282Y and C282Y/H63D
- Non-HFE-related hemochromatosis, which includes mutations in genes such as:
- Hemojuvelin (HJV)
- Transferrin receptor-2 (TfR2)
- Ferroportin (SLC40A1)
- Hepcidin (HAMP) These forms of hemochromatosis are distinct from secondary iron overload, which can result from various conditions including iron-loading anemias, chronic liver disease, and parenteral iron overload 1. It's worth noting that the diagnosis and management of hemochromatosis have been outlined in practice guidelines, such as those published by the American Association for the Study of Liver Diseases in 2011 1, which provide a framework for understanding the different types of hereditary hemochromatosis and their underlying genetic causes. The most recent and highest quality study on this topic is the 2011 practice guideline by the American Association for the Study of Liver Diseases 1, which provides a comprehensive overview of the classification and management of hereditary hemochromatosis.
From the Research
Types of Hereditary Hemochromatosis (HH)
- Classical HH is associated with mutations in the HFE gene, specifically C282Y homozygotes or C282Y/H63D compound heterozygotes 2, 3, 4, 5
- Non-HFE associated HH is caused by mutations in other genes involved in iron metabolism, such as the SLC40A1 gene encoding the iron exporter ferroportin 6, 2
- Juvenile and TFR2-related hemochromatoses are types of non-HFE hemochromatosis that show recessive inheritance, increased transferrin saturation, iron storage in hepatocytes, and responsiveness to phlebotomy 6
- Ferroportin disease is a type of hemochromatosis caused by autosomal dominant mutations in the SLC40A1 gene, characterized by iron loading of Kupffer cells and normal transferrin saturation 6
Subgroups of Hemochromatosis
- The first subgroup includes juvenile and TFR2-related hemochromatoses, which are due to hepcidin deficiency or the inability to increase hepcidin levels according to iron stores 6
- The second subgroup is caused by autosomal dominant mutations in the SLC40A1 gene, leading to a hemochromatosis-like phenotype with dominant inheritance 6