From the Guidelines
Yes, it is possible to have non-genetic hemochromatosis, which is called secondary or acquired hemochromatosis. This condition occurs when iron builds up in the body due to factors other than inherited genetic mutations. According to the 2011 practice guideline by the American Association for the Study of Liver Diseases 1, secondary iron overload can be caused by various factors, including:
- Iron-loading anemias, such as thalassemia major, sideroblastic anemia, and chronic hemolytic anemia
- Parenteral iron overload, which can occur due to red blood cell transfusions, iron-dextran injections, or long-term hemodialysis
- Chronic liver diseases, such as alcoholic liver disease, hepatitis C, hepatitis B, and nonalcoholic fatty liver disease
- Miscellaneous causes, including neonatal iron overload, aceruloplasminemia, and congenital atransferrinemia
These causes of secondary iron overload are distinct from hereditary hemochromatosis, which is caused by genetic mutations, such as those in the HFE gene 1. Secondary hemochromatosis typically develops as a complication of other medical conditions or treatments, and its treatment involves addressing the underlying cause while managing iron levels through phlebotomy or iron chelation therapy. It is essential to note that oral iron ingestion does not typically lead to iron overload except in genetically predisposed individuals or those with ineffective erythropoiesis 1.
From the Research
Non-Genetic Hemochromatosis
- There is no direct evidence to suggest the existence of non-genetic (not inherited) hemochromatosis, as all forms of hemochromatosis mentioned in the studies are related to genetic mutations 2, 3, 4, 5.
- The studies focus on hereditary hemochromatosis, which is an autosomal recessive disorder caused by mutations in genes such as HFE, Hamp, HJV, TFR2, and SCL40A1 2, 4, 5.
- Non-HFE hemochromatosis refers to forms of hereditary hemochromatosis that are not caused by mutations in the HFE gene, but rather by mutations in other genes involved in iron metabolism 2, 4, 5.
- The clinical manifestations and management of non-HFE hemochromatosis are similar to those of HFE-related hemochromatosis, with periodic phlebotomies being the primary treatment 2, 3.
Genetic Forms of Hemochromatosis
- HFE-related hemochromatosis is the most common form of hereditary hemochromatosis, accounting for 80-90% of cases 3, 5.
- Non-HFE hemochromatosis accounts for around 20% of cases and is caused by mutations in genes such as HJV, HAMP, TFR2, and SLC40A1 4, 5.
- The clinical onset and phenotypic expressivity of non-HFE hemochromatosis can vary depending on the affected gene and its role in iron trafficking 4.
Diagnosis and Management
- Diagnosis of hereditary hemochromatosis requires confirmation of increased serum ferritin levels and transferrin saturation, with or without symptoms 3.
- Subtyping is based on genotypic expression, and serum ferritin measurement is the most useful prognostic indicator of disease severity 3, 6.
- Treatment of hereditary hemochromatosis involves periodic phlebotomies, with the frequency guided by serial measurements of serum ferritin levels and transferrin saturation 2, 3.