Which are the causes of HFE hereditary haemochromatosis?

Hereditary haemochromatosis (HFE) is a genetic disorder characterized by excessive absorption and accumulation of iron in the body. It is primarily caused by mutations in the HFE gene, which is responsible for regulating iron levels in the body. HFE hereditary haemochromatosis is the most common form of iron overload disorder, affecting individuals of European descent more frequently than other populations.

The HFE gene mutations associated with hereditary haemochromatosis are primarily C282Y and H63D. The C282Y mutation is the most common and severe form, while the H63D mutation is less common and generally milder in its effects. These mutations disrupt the normal function of the HFE protein, leading to increased absorption of dietary iron from the intestines.

Iron overload occurs gradually over time in individuals with HFE hereditary haemochromatosis. The excessive iron is stored in various organs, particularly the liver, heart, pancreas, and joints. If left untreated, the accumulated iron can cause damage to these organs, leading to serious health complications.

Hereditary haemochromatosis is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated HFE gene (one from each parent) to develop the condition. If an individual inherits only one mutated gene, they are considered carriers and may have a slightly increased risk of iron overload but are unlikely to develop symptoms.

Family history plays a significant role in the development of hereditary haemochromatosis. If both parents carry a mutated HFE gene, each child has a 25% chance of inheriting two copies and developing the disorder. However, not all individuals with two copies of the mutated gene will develop symptoms, as other factors such as environmental influences and additional genetic variations can influence disease expression.

Gender also plays a role in the manifestation of HFE hereditary haemochromatosis. Men are more likely to develop symptoms and experience iron overload at an earlier age compared to women. This difference is believed to be influenced by hormonal factors, as women tend to lose iron through menstruation and childbirth.

Although HFE gene mutations are the primary cause of hereditary haemochromatosis, other genetic and environmental factors can influence disease severity and progression. Variations in other genes involved in iron metabolism, such as HAMP and TFR2, can modify the effects of HFE mutations. Additionally, factors like excessive alcohol consumption, certain liver diseases, and a diet high in iron can exacerbate iron overload in individuals with HFE hereditary haemochromatosis.

Early detection and treatment are crucial in managing hereditary haemochromatosis. Regular screening for iron overload, particularly in individuals with a family history of the disorder, can help identify those at risk. Treatment typically involves therapeutic phlebotomy, a process of regularly removing blood to reduce iron levels. Dietary modifications, such as reducing iron-rich foods and avoiding vitamin C supplements, may also be recommended to limit iron absorption.

In conclusion, hereditary haemochromatosis is primarily caused by mutations in the HFE gene, leading to excessive iron absorption and accumulation in the body. Family history, gender, and other genetic and environmental factors can influence disease expression and severity. Early detection and appropriate management are essential in preventing complications associated with iron overload.