From the Guidelines
The HFE gene is a crucial gene that regulates iron absorption in the body, and mutations in this gene, particularly C282Y and H63D, are associated with hereditary hemochromatosis, a common inherited iron overload disorder. The HFE gene produces a protein that helps control how much iron is absorbed from food in the intestines. According to 1, mutations in the HFE gene are responsible for hereditary hemochromatosis, which can lead to serious health problems, including liver cirrhosis, diabetes, heart problems, joint pain, and skin darkening. The most frequent mutations are C282Y and H63D, with C282Y homozygosity being the most clinically significant, as it is present in almost 90% of those affected, as stated in 1.
Some key points to consider about the HFE gene and hereditary hemochromatosis include:
- The condition is particularly common in people of Northern European descent, affecting about 1 in 200-300 individuals, as mentioned in 1.
- The diagnosis of hereditary hemochromatosis is typically made through blood tests measuring iron levels and genetic testing for HFE mutations, as discussed in 1.
- Treatment usually involves regular blood removal (phlebotomy) to reduce iron levels in the body, as noted in 1.
- Early diagnosis and treatment are crucial to prevent long-term complications, such as organ damage and increased risk of hepatocellular cancer, as highlighted in 1.
Overall, understanding the role of the HFE gene in iron absorption and its association with hereditary hemochromatosis is essential for early diagnosis and effective management of this condition, as emphasized in 1 and 1.
From the Research
Definition and Function of the HFE Gene
- The HFE gene is associated with hereditary hemochromatosis, an autosomal recessive genetic disease characterized by excessive iron absorption 2, 3, 4, 5, 6.
- The HFE gene influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism 4.
- Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent 4.
Structure and Mutations of the HFE Gene
- The HFE gene is linked to the major histocompatibility complex (MHC) on chromosome 6p and encodes the MHC class I-like protein HFE that binds beta-2 microglobulin 4.
- Genetic polymorphisms of the HFE gene, such as rs1800562, rs1799945, and rs1800730, affect the normal activity of hepcidin 2.
- The C282Y mutation of the HFE gene is the most common cause of hereditary hemochromatosis, accounting for 85-90% of phenotypically affected individuals 6.
Clinical Significance of the HFE Gene
- Hereditary hemochromatosis can lead to morbidity and eventually death if left untreated, with clinical onset symptoms occurring more frequently in adult men than women 2.
- Early detection of HFE gene mutations can prevent the progression of iron accumulation and contribute to achieving normal life expectancy 2.
- Screening for HFE mutations is recommended for first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results 6.