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, can lead to hereditary hemochromatosis, a genetic iron overload disorder. Located on chromosome 6, the HFE gene plays a vital role in preventing excessive iron absorption from food, which can accumulate in tissues and organs, particularly the liver, heart, and pancreas, leading to serious complications such as liver disease, diabetes, heart problems, joint pain, and skin darkening 1. Hereditary hemochromatosis is an autosomal recessive condition, meaning a person must inherit two mutated copies of the gene (one from each parent) to develop the full disorder, though carriers with one mutation may have milder iron regulation issues 1.
Key Points
- The HFE gene is responsible for regulating iron absorption in the body
- Mutations in the HFE gene, particularly C282Y and H63D, can lead to hereditary hemochromatosis
- Hereditary hemochromatosis is an autosomal recessive condition that can cause serious complications if left untreated
- Early detection of HFE mutations allows for simple treatment through regular blood removal (phlebotomy) to prevent organ damage 1
Diagnosis and Management
The diagnosis of hereditary hemochromatosis is usually based on a combination of genetic and phenotypic criteria, including direct DNA testing for HFE gene mutations and measurement of transferrin saturation and serum ferritin levels 1. Liver biopsy to measure hepatic iron concentration is considered the gold standard for diagnosis, but genetic testing has become a more widely used and non-invasive alternative 1.
Treatment and Prevention
Early detection and treatment of hereditary hemochromatosis can prevent organ damage and improve quality of life. Regular blood removal (phlebotomy) is a simple and effective treatment for removing excess iron from the body and preventing complications 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.