Haemochromatosis
Disease Details
Family Health Simplified
- Description
- Haemochromatosis is a genetic disorder characterized by excessive iron absorption and accumulation in the body, leading to potential organ damage.
- Type
- Haemochromatosis is typically classified as a type of genetic disorder known as an autosomal recessive condition. This means that an individual must inherit two copies of the defective gene, one from each parent, to express the disease. The gene most commonly associated with haemochromatosis is the HFE gene, specifically mutations known as C282Y and H63D.
- Signs And Symptoms
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Organs most commonly affected by hemochromatosis include the liver, heart, and endocrine glands.Hemochromatosis may present with the following clinical syndromes:
liver: chronic liver disease and cirrhosis of the liver.
heart: heart failure, cardiac arrhythmia.
hormones: diabetes (see below) and hypogonadism (insufficiency of the sex hormone producing glands) which leads to low sex drive and/or loss of fertility in men and loss of fertility and menstrual cycle in women.
metabolism: diabetes in people with iron overload occurs as a result of selective iron deposition in islet beta cells in the pancreas leading to functional failure and cell death.
skeletal: arthritis, from iron deposition in joints leading to joint pains. The most commonly affected joints are those of the hands, particularly the knuckles or metacarpophalangeal joints, wrists or radiocarpal joints, elbow, hip, knee and ankle joints. Risk factors for the development of arthritis in those with hemochromatosis include elevated iron levels (ferritin greater than 1000 or transferrin saturation greater than 50%) for an extended period of time, increasing age and concurrent advanced liver fibrosis.
skin: melanoderma (darkening or 'bronzing' of the skin).Hemochromatosis leading to secondary diabetes (through iron deposition in the insulin secreting beta cells of the pancreas), when combined with a bronzing or darkening of the skin, is sometimes known as "bronze diabetes". - Prognosis
- In general, provided there has been no liver damage, patients should expect a normal life expectancy if adequately treated by venesection. If the serum ferritin is greater than 1,000 µg/L at diagnosis there is a risk of liver damage and cirrhosis which may eventually shorten their life. The presence of cirrhosis increases the risk of hepatocellular carcinoma. Other risk factors for liver damage in hemochromatosis include alcohol use, diabetes, liver iron levels greater than 2,000 μmol/gram and increased aspartate transaminase levels.The risk of death and liver fibrosis are elevated in males with HFE type hemochromatosis but not in females; this is thought to be due to a protective effect of menstruation and pregnancy seen in females as well as possible hormone-related differences in iron absorption.
- Onset
- Hemochromatosis typically has an onset in adulthood, often between the ages of 30 and 50 for men and after menopause for women, as iron accumulates slowly over time.
- Prevalence
- Hereditary hemochromatosis is one of the most common genetic disorders in people of Northern European descent. The prevalence of homozygosity for the HFE gene mutation (C282Y variant) is approximately 1 in 200 to 1 in 300 individuals in this population. Heterozygosity for the mutation is more common, affecting about 1 in 8 to 1 in 10 people. The condition can lead to iron overload, potentially causing tissue and organ damage if untreated.
- Epidemiology
- HHC is most common in certain European populations (such as those of Irish or Scandinavian descent) and occurs in 0.6% of some unspecified population. Men have a 24-fold increased rate of iron-overload disease compared with women.
- Intractability
- Hemochromatosis is generally not considered intractable. It is a manageable condition, particularly if diagnosed early. Treatment typically involves phlebotomy (regular blood removal) to reduce iron levels, and managing diet to limit iron intake. Early intervention can prevent serious complications and allow individuals to lead normal lives.
- Disease Severity
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Haemochromatosis is a genetic disorder that causes the body to absorb too much iron from the diet. Over time, the excess iron levels can lead to severe complications if left untreated. The severity of the disease varies among individuals and depends on factors such as the extent of iron overload and the presence of organ damage.
- **Disease Severity:** Haemochromatosis can range from mild to severe. In its early stages, individuals may be asymptomatic or experience nonspecific symptoms such as fatigue or joint pain. If the condition progresses without treatment, it can lead to significant complications including liver cirrhosis, diabetes, heart disease, and arthritis, among others. Early diagnosis and management are crucial to prevent these severe outcomes. - Healthcare Professionals
- Disease Ontology ID - DOID:2352
- Pathophysiology
- Defects in iron metabolism, specifically involving the iron regulatory protein hepcidin are thought to play an integral role in the pathogenesis of hereditary hemochromatosis.Normally, hepcidin acts to reduce iron levels in the body by inhibiting intestinal iron absorption and inhibiting iron mobilization from stores in the bone marrow and liver. Iron is absorbed from the intestines (mostly in the duodenum) and transported across intestinal enterocytes or mobilized out of storage in liver hepatocytes or from macrophages in the bone marrow by the transmembrane ferroportin transporter. In response to elevated plasma iron levels, hepcidin inhibits the ferroportin transporter leading to decreased iron mobilization from stores and decreased intestinal iron absorption, thus functioning as a negative iron regulatory protein.In hereditary hemochromatosis, mutations in the proteins involved in hepcidin production including HFE (hemostatic iron regulator), hemojuvelin and transferrin receptor 2 lead to a loss or decrease in hepcidin production, which subsequently leads to the loss of the inhibitory signal regulating iron absorption and mobilization and thus leads to iron overload. In very rare instances, mutations in ferroportin result in ferroportin resistance to hepcidin's negative regulatory effects, and continued intestinal iron absorption and mobilization despite inhibitory signaling from hepcidin. Approximately 95% of cases of hereditary hemochromatosis are due to mutations in the HFE gene.The resulting iron overload causes iron to deposit in various sites throughout the body, especially the liver and joints, which coupled with oxidative stress leads to organ damage or joint damage and the pathological findings seen in hemochromatosis.
- Carrier Status
- Carrier status for haemochromatosis generally refers to individuals who inherit one mutated copy of the HFE gene (most commonly the C282Y mutation) associated with the condition. Carriers typically do not develop symptoms of haemochromatosis but can pass the mutated gene to their offspring. If both parents are carriers, there is a 25% chance their child will have haemochromatosis, a 50% chance their child will be a carrier, and a 25% chance their child will not inherit the mutated gene.
- Mechanism
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Hemochromatosis is a genetic disorder characterized by excessive iron absorption and accumulation in the body, leading to tissue and organ damage.
**Mechanism:**
In individuals with hemochromatosis, the small intestine absorbs more iron than the body needs. Normally, iron absorption is tightly regulated by the hormone hepcidin, which is produced by the liver. Hepcidin inhibits iron absorption by binding to and inducing the degradation of ferroportin, an iron transporter on the surface of enterocytes (intestinal cells) and macrophages. In hemochromatosis, this regulation is disrupted, leading to excessive iron absorption and deposition in tissues such as the liver, heart, and pancreas. This iron overload can cause organ dysfunction and damage over time.
**Molecular Mechanisms:**
Hemochromatosis is most commonly associated with mutations in the HFE gene, although mutations in other genes like HJV, HAMP, and TFR2 can also cause the disorder.
1. **HFE Gene Mutation:**
- The most common mutation in the HFE gene associated with hemochromatosis is the C282Y mutation. Another mutation, H63D, can also contribute to the disorder when present in combination with C282Y.
- The HFE protein normally interacts with the transferrin receptor to regulate iron uptake by cells. Mutations in the HFE gene impair this interaction, leading to decreased hepcidin production. Reduced hepcidin levels result in unchecked ferroportin activity, increasing iron absorption from the gut.
2. **HJV (Hemojuvelin) and HAMP (Hepcidin Antimicrobial Peptide):**
- Mutations in HJV or HAMP genes can lead to early-onset or juvenile hemochromatosis.
- Hemojuvelin is a co-receptor involved in the bone morphogenetic protein (BMP) signaling pathway, which regulates hepcidin expression. Mutations in HJV disrupt this pathway, reducing hepcidin levels.
- Mutations in HAMP directly affect the production of hepcidin, decreasing its levels and leading to increased iron absorption.
3. **TFR2 (Transferrin Receptor 2):**
- TFR2 mutations are associated with a rarer form of hemochromatosis.
- TFR2 is involved in sensing body iron levels and regulating hepcidin expression. Mutations in TFR2 impair this sensing mechanism, reducing hepcidin production and increasing iron absorption.
The excess iron from hemochromatosis deposits in various organs, leading to conditions such as liver cirrhosis, diabetes, heart disease, and arthritis as the iron damages tissues over time. Early diagnosis and management are crucial to prevent these complications. - Treatment
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For hemochromatosis, treatment primarily involves:
1. **Phlebotomy**: Regularly scheduled blood removal to reduce iron levels.
2. **Chelation Therapy**: Medication to bind excess iron and promote its excretion, typically used if phlebotomy is not an option.
3. **Dietary Changes**: Avoiding iron supplements and reducing dietary iron intake, particularly from red meat and fortified foods.
4. **Monitoring and Management**: Regular monitoring of iron levels, liver function, and associated complications, such as liver disease or diabetes.
No immediate information about "nan" is relevant to the treatment of hemochromatosis. If this refers to something specific, further context is needed. - Compassionate Use Treatment
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Hemochromatosis primarily involves the accumulation of excess iron in the body. While the mainstay treatment is phlebotomy (regular blood removal), some experimental or off-label treatments include:
1. **Deferoxamine**: An iron chelator typically used to manage iron overload in conditions like thalassemia. Its use in hemochromatosis is not standard but is being explored in circumstances where phlebotomy is not feasible.
2. **Deferiprone and Deferasirox**: Oral iron chelators being studied in off-label contexts.
3. **Erythrocytapheresis**: An advanced form of bloodletting that removes red blood cells more efficiently. It may be considered for patients unable to tolerate traditional phlebotomy.
4. **Hepcidin Mimetics and Agonists**: These are experimental therapies aimed at regulating hepcidin, a hormone that controls iron absorption. Researchers are investigating their potential to correct iron overload.
These treatments are still under investigation, and their safety and efficacy profiles are not fully established. Always consult with a healthcare provider before considering any off-label or experimental treatments. - Lifestyle Recommendations
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For haemochromatosis, lifestyle recommendations include:
1. **Dietary Changes**:
- Avoid iron-rich foods such as red meat, liver, and iron-fortified foods.
- Limit alcohol intake, as it can increase iron absorption and liver damage.
- Avoid vitamin C supplements, which can increase iron absorption.
2. **Regular Monitoring**:
- Routine blood tests to monitor iron levels and overall health.
- Regular consultations with a healthcare provider to manage the condition.
3. **Phlebotomy (Therapeutic Blood Removal)**:
- Regularly scheduled phlebotomy to reduce iron levels in the body as recommended by a healthcare professional.
4. **Avoid Iron Supplements**:
- Steer clear of multivitamins and supplements that contain iron.
5. **Stay Hydrated**:
- Drink plenty of water to help maintain overall health and organ function.
6. **Exercise**:
- Engage in regular, moderate exercise to maintain overall health without overexerting the body.
Following these recommendations can help manage haemochromatosis and prevent complications. - Medication
- Medications are used for those unable to tolerate routine blood draws, there are chelating agents available for use. The drug deferoxamine binds with iron in the bloodstream and enhances its elimination in urine and faeces. Typical treatment for chronic iron overload requires subcutaneous injection over a period of 8–12 hours daily. Two newer iron-chelating drugs that are licensed for use in patients receiving regular blood transfusions to treat thalassaemia (and, thus, who develop iron overload as a result) are deferasirox and deferiprone.
- Repurposable Drugs
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Haemochromatosis is a condition characterized by excessive iron accumulation in the body. While the primary treatment for haemochromatosis is therapeutic phlebotomy (regular blood removal), some drugs used for other conditions have shown potential for managing iron levels:
1. **Deferoxamine** - Originally used for conditions causing iron overload like transfusion-related hemosiderosis, this iron-chelating agent can help reduce iron levels in haemochromatosis patients who cannot undergo phlebotomy.
2. **Deferasirox** - Another iron chelator, commonly used in patients with blood disorders like thalassemia, can be repurposed to manage iron overload.
3. **Deferiprone** - This oral iron chelator is often used for patients with thalassemia and may also help haemochromatosis patients when phlebotomy is contraindicated.
Research is ongoing to find more effective pharmacological treatments for haemochromatosis, including exploring the repurposing of existing medications. - Metabolites
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In haemochromatosis, which is a condition characterized by excessive iron accumulation in the body, key metabolites affected include:
1. **Iron:** Elevated levels in blood serum.
2. **Ferritin:** Elevated, as it reflects iron stores in the body.
3. **Transferrin Saturation:** Increased due to the higher availability of iron.
4. **Liver Enzymes:** Often elevated due to liver damage caused by iron overload.
Metabolite levels can significantly influence the progression and management of haemochromatosis. - Nutraceuticals
- For haemochromatosis, nutraceuticals generally refer to food products or supplements that offer medical or health benefits. However, managing haemochromatosis primarily involves dietary adjustments to limit iron intake due to the body's tendency to absorb too much iron. Therefore, specific nutraceuticals are typically not recommended. Instead, patients are advised to avoid iron supplements, vitamin C supplements (which increase iron absorption), and to be cautious with alcohol consumption, as it can increase iron absorption and damage the liver. Regular monitoring and medical treatment, such as phlebotomy, are essential in managing the condition. Always consult a healthcare provider before making any changes to your diet or supplement regimen.
- Peptides
- For haemochromatosis, peptides do not play a central role in its pathogenesis or treatment. Hemochromatosis is primarily associated with genetic mutations, often in the HFE gene, which leads to excessive iron absorption and accumulation in the body. The treatment usually involves regular phlebotomies (blood removal) to reduce iron levels. Nanotechnology is not typically part of standard care for haemochromatosis but is an area of ongoing research for potential diagnostic and therapeutic advancements.