hemochromatosis type 2B

Hemochromatosis Type 2B: A Rare Genetic Disorder

Hemochromatosis type 2B, also known as HAMP-related juvenile hemochromatosis, is a rare genetic disorder characterized by excessive iron accumulation in various organs of the body. This condition typically affects individuals in their first to third decades of life and can lead to severe iron overload, organ damage, and failure.

Key Features:

• Age of onset: Typically occurs in the first to third decades of life
• Sex distribution: Males and females are equally affected
• Iron accumulation: Excessive iron deposition in various organs, leading to tissue damage and organ failure
• Clinical features: May include hypogonadotropic hypogonadism, cardiomyopathy, glucose intolerance and diabetes, arthropathy, and liver fibrosis or cirrhosis

Genetic Cause:

Hemochromatosis type 2B is caused by homozygous mutations in the HAMP gene (606464) on chromosome 19q13. This genetic mutation leads to impaired hepcidin production, resulting in excessive iron absorption and accumulation.

Classification:

Type 2 hemochromatosis or juvenile hemochatosis is subclassified into type 2a, which is associated with mutations in hemojuvelin, and type 2B, which is associated with mutations in hepcidin. Both conditions can present before the third decade, and affected patients are at high risk of developing target organ damage, including cardiomyopathy.

References:

• [11] Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life.
• [13] Type 2 hemochromat

Early symptoms of Hemochromatosis type 2 typically include liver disease, heart disease, and low levels of sex hormones [1]. Having low levels of sex hormones can lead to various symptoms in both males and females.

Some common signs and symptoms of hemochromatosis type 2B may include:

• Liver damage (cirrhosis): This is a serious condition where the liver becomes scarred, leading to potential liver failure [6].
• Joint pains: Hemochromatosis can cause joint pain and arthritis due to iron buildup in the joints [9][10].
• Changes in skin coloration: People with hemochromatosis type 2B may experience changes in skin pigmentation, which can be a sign of iron overload [6].
• Heart failure: Untreated hemochromatosis can lead to heart disease and potentially fatal heart conditions [7].
• Diabetes mellitus: Hemochromatosis has been linked to an increased risk of developing diabetes [6][10].
• Sexual dysfunction: Males may experience delayed puberty or symptoms related to a shortage of sex hormones, while females may experience hypogonadotropic hypogonadism [4][5].

It's essential to note that these symptoms can vary in severity and presentation. If you suspect you or someone else has hemochromatosis type 2B, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References: [1] - Early symptoms of hereditary hemochromatosis may include extreme tiredness (fatigue), joint pain, abdominal pain, weight loss, and loss of sex hormones. [4] - Common symptoms include absent or decreased function of the testes in males or ovaries in females (hypogonadotropic hypogonadism), heart (... [5] - Jan 6, 2023 — Symptoms · Joint pain. · Abdominal pain. · Fatigue. · Weakness. · Diabetes. · Loss of sex drive. · Impotence. · Heart failure. [6] - Sep 5, 2024 — Signs of iron overload may include liver damage (cirrhosis), joint pains, changes in skin coloration, heart failure, diabetes mellitus, sexual ... [7] - Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If type 2 hemochromatosis is untreated, potentially fatal heart disease ... [9] - Jun 8, 2023 — The most common signs at the time of presentation are hepatomegaly (13%), skin pigmentation, and arthritis. See Presentation for more detail. [10] - Hemochromatosis Symptoms · Weakness and fatigue · Increased skin pigmentation · Hair loss · Impotence and loss of sex drive · Joint pains · Memory loss.

Hemochromatosis type 2B, also known as juvenile hemochromatosis, is a rare genetic disorder characterized by excessive iron accumulation in the body. Diagnosing this condition can be challenging due to its rarity and similarity in symptoms with other conditions.

Initial Testing

The initial testing for hemochromatosis involves assessing iron overload via serum transferrin saturation (TSAT), which is calculated from serum iron and iron binding capacity [4][8]. This test measures the amount of iron bound to transferrin, a protein that carries iron in the blood. Elevated TSAT levels indicate iron overload.

Blood Tests

Blood tests are essential for diagnosing hemochromatosis type 2B. The most important initial tests include:

• Serum ferritin: This test measures the amount of iron stored in the liver [9].
• Serum iron: Tests how much iron is in your blood [9].
• Transferrin saturation test (TSAT): Measures the percentage of transferrin that is saturated with iron [4][8].

Genetic Testing

Genetic testing is recommended for all parents, siblings, and children of anyone diagnosed with hemochromatosis type 2B. This is because hemochromatosis is an inherited condition, and identifying genetic mutations can confirm the diagnosis [1]. Gene assay is diagnostic of hereditary hemochromatosis caused by HFE gene mutations [3].

Other Diagnostic Tests

In cases where ferritin and iron blood tests indicate iron overload but genetic testing is negative for the HFE gene mutation, other diagnostic tests may be performed to rule out other conditions. These include:

• Liver biopsy: A liver biopsy can confirm iron accumulation in the liver.
• Imaging studies: Imaging studies such as MRI or CT scans may be used to assess organ damage.

Early Detection

Early detection and treatment of hemochromatosis type 2B are crucial for preventing morbidity and mortality. Regular blood tests and genetic testing can help identify individuals at risk, allowing for early intervention and reducing the risk of complications [1].

References:

[1] GeneReview: Hemochromatosis [3] Gene assay is diagnostic of hereditary hemochromatosis caused by HFE gene mutations [4] Serum transferrin saturation (TSAT) test [8] Blood tests for diagnosing hemochromatosis type 2B [9] Serum ferritin and serum iron tests

Treatment Options for Hemochromatosis Type 2B

Hemochromatosis type 2B, also known as juvenile hemochromatosis, is a rare genetic disorder characterized by excessive iron accumulation in the body. While phlebotomy (blood removal) remains the standard treatment for this condition, drug therapy can be used to manage symptoms and prevent complications.

Medications Used

• Deferasirox: This oral chelating agent is commonly used to treat hemochromatosis type 2B. It works by binding to iron and allowing it to be excreted from the body [4][5].
• Desferrioxamine: Another chelating agent, desferrioxamine can be administered intravenously or subcutaneously to remove excess iron from the body [3].

Treatment Goals

The primary goal of drug treatment in hemochromatosis type 2B is to reduce iron levels and prevent organ damage. Regular monitoring of serum ferritin, iron, and transferrin saturation levels can help guide treatment decisions.

Additional Considerations

• Phlebotomy: While not always necessary, phlebotomy may be recommended in conjunction with drug therapy to remove excess iron from the body [6].
• Antidotes for iron toxicity: In cases of significant anemia or severe end-organ involvement, antidotes for iron toxicity may be used to manage symptoms [7].

References

[3] Commonly used medicines are deferasirox and desferrioxamine. Deferasirox is unlicensed for the treatment of haemochromatosis, which means it has not undergone ...

[4] Jun 8, 2023 — Deferasirox (Exjade) is the oral iron chelator that should be taken once daily as an adjunct to phlebotomies or instead of phlebotomy in ...

[5] Drugs used to treat Hemochromatosis ; Generic name: deferasirox systemic; Drug class: chelating agents; For consumers: dosage, interactions, side effects; For ...

[6] Sep 5, 2024 — Treatment typically involves regular phlebotomy (removal of blood) since red blood cells contain a large amount of the body's iron.

[7] Jun 8, 2023 — Antidotes for iron toxicity are used in patients with hemochromatosis that is associated with significant anemia or severe end-organ involvement.

Hereditary hemochromatosis type 2B, also known as juvenile hemochromatosis, is a rare genetic disorder characterized by the accumulation of iron in various organs of the body. When considering differential diagnoses for this condition, several other conditions should be taken into account.

• Alcoholic liver disease: This condition can present with similar symptoms to hereditary hemochromatosis type 2B, including elevated liver enzymes and abnormal iron study results [7].
• Nonalcoholic fatty liver disease (NAFLD): NAFLD is a condition characterized by excessive fat accumulation in the liver, which can be associated with elevated serum ferritin levels, similar to hereditary hemochromatosis type 2B [5].
• Post-transfusional iron overload: This condition occurs when there is an excess of iron in the body due to repeated blood transfusions, such as in patients with hematological diseases like thalassemia [8].
• TFR2-related hemochromatosis: This is another form of hereditary hemochromatosis that can present with similar symptoms to type 2B, including excessive iron accumulation and tissue damage.
• Iron-loading anemias: Certain types of anemia, such as thalassemia major, can lead to iron overload in the body, which may be mistaken for hereditary hemochromatosis type 2B [9].

It's essential to consider these differential diagnoses when evaluating patients with suspected hereditary hemochromatosis type 2B. A comprehensive diagnostic workup, including genetic testing and iron studies, can help differentiate between these conditions.

References: [5] - Elevated serum ferritin is seen in many other conditions and is often present in patients with nonalcoholic fatty liver disease or alcohol-related liver disease. [7] - Hereditary hemochromatosis should be considered in the differential diagnosis of patients with elevated liver enzymes and abnormal iron study results. [8] - Differential diagnosis includes TFR2-related hemochromatosis and post-transfusional iron overload in the case of hematological diseases such as thalassemia. [9] - Important differential diagnoses for haemochromatosis include alcohol- or metabolic-dysfunction associated fatty liver disease, and iron-loading anemias.