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Thalassemia

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Description: Thalassemia is a genetic blood disorder characterized by reduced hemoglobin production, leading to anemia and other health complications.
Type: Thalassemia is a blood disorder characterized by the body’s inability to produce adequate hemoglobin. There are two main types of thalassemia: Alpha thalassemia and Beta thalassemia.

- **Alpha thalassemia**: Caused by mutations in the HBA1 and HBA2 genes, which affect the production of alpha-globin chains.
- **Beta thalassemia**: Caused by mutations in the HBB gene, affecting the production of beta-globin chains.

**Type of genetic transmission**: Thalassemia is inherited in an autosomal recessive pattern. This means that a person must inherit two copies of the mutated gene, one from each parent, to manifest the disease. Carriers, who have only one copy of the mutated gene, usually do not exhibit symptoms but can pass the mutated gene to their offspring.
Signs And Symptoms: Iron overload: People with thalassemia can get an overload of iron in their bodies, either from the disease itself or from frequent blood transfusions. Too much iron can result in damage to the heart, liver, and endocrine system, which includes glands that produce hormones that regulate processes throughout the body. The damage is characterized by excessive deposits of iron. Without adequate iron chelation therapy, almost all patients with beta-thalassemia accumulate potentially fatal iron levels.
Infection: People with thalassemia have an increased risk of infection. This is especially true if the spleen has been removed.
Bone deformities: Thalassemia can make the bone marrow expand, which causes bones to widen. This can result in abnormal bone structure, especially in the face and skull. Bone marrow expansion also makes bones thin and brittle, increasing the risk of broken bones.
Enlarged spleen: The spleen aids in fighting infection and filters unwanted material, such as old or damaged blood cells. Thalassemia is often accompanied by the destruction of a large number of red blood cells and the task of removing these cells causes the spleen to enlarge. Splenomegaly can make anemia worse, and it can reduce the life of transfused red blood cells. Severe enlargement of the spleen may necessitate its removal.
Slowed growth rates: anemia can cause the growth of a child to slow down. Puberty may also be delayed in children with thalassemia.
Heart problems: Diseases, such as congestive heart failure and abnormal heart rhythms, may be associated with severe thalassemia.
Prognosis: Thalassemia is a genetic blood disorder that affects the body's ability to produce hemoglobin and red blood cells. The prognosis for individuals with thalassemia varies depending on the type and severity of the disorder:

1. **Thalassemia Minor (Trait)**:
- Individuals typically have mild anemia or no symptoms.
- Life expectancy is usually normal.
- Requires minimal to no treatment.

2. **Thalassemia Intermedia**:
- Symptoms can range from mild to moderate anemia.
- Regular monitoring and occasional blood transfusions may be necessary.
- Life expectancy can be near normal with appropriate medical care.

3. **Thalassemia Major (Cooley's Anemia)**:
- Severe form with serious symptoms appearing within the first two years of life.
- Requires regular blood transfusions and possible bone marrow or stem cell transplants.
- Complications from treatment, such as iron overload, need to be managed effectively.
- Life expectancy has improved with advanced treatments and is often into the mid-40s to 60s or longer, depending on management and individual health factors.

Overall, early diagnosis and ongoing medical care significantly improve the quality of life and prognosis for individuals with thalassemia.
Onset: Thalassemia onset typically occurs in childhood. Symptoms may not be apparent until a few months after birth.
Prevalence: Thalassemias are a group of inherited blood disorders characterized by abnormal hemoglobin production. The prevalence of thalassemia varies greatly worldwide but tends to be higher in regions where malaria is or was historically prevalent, such as the Mediterranean, Middle East, South Asia, and parts of Africa. The global carrier rate for beta-thalassemia, one of the most common forms, is estimated to be 1.5%, affecting millions of individuals. However, specific prevalence rates can vary significantly from country to country and even within regions.
Epidemiology: The beta form of thalassemia is particularly prevalent among Mediterranean peoples, and this geographical association is responsible for its original name. Thalassemia resulted in 25,000 deaths in 2013 down from 36,000 deaths in 1990.In Europe, the highest concentrations of the disease are found in Greece, coastal regions in Turkey (particularly the Aegean Region such as İzmir, Balıkesir, Aydın, Muğla, and Mediterranean Region such as Antalya, Adana, Mersin), in southern Spain, in parts of Italy, particularly southern Italy. With the exception of the Balearics, the major Mediterranean Islands, such as Sicily, Sardinia, Malta, Corsica, Cyprus, and Crete are heavily affected. Other Mediterranean peoples, as well as those in the vicinity of the Mediterranean, also have high rates of thalassemia, including people from North Africa and West Asia. Far from the Mediterranean, South Asians are also affected, with the world's highest concentration of carriers (16–18% of the population) in the Maldives.The disease is also found in populations living in Africa, the Americas, and in Tharu people in the Terai region of Nepal and India. It is believed to account for much lower rates of malaria illnesses and deaths, accounting for the historic ability of Tharus to survive in areas with heavy malaria infestation while others could not. Thalassemias are particularly associated with people of Mediterranean origin, Arabs (especially Palestinians and people of Palestinian descent), and Asians. The estimated prevalence is 16% in people from Cyprus, 1% in Thailand, and 3–8% in populations from Bangladesh, China, India, Malaysia and Pakistan.
Estimates suggest that approximately 1.5% of the global population (80 – 90 million people) are β-thalassemia carriers. However, exact data on carrier rates in many populations are lacking, particularly in developing areas of the world known or expected to be heavily affected. Because of the prevalence of the disease in countries with little knowledge of thalassemia, access to proper treatment and diagnosis can be difficult. While there are some diagnostic and treatment facilities in developing countries, in most cases these are not provided by government services and are available only to patients who can afford them. In general, poorer populations only have access to limited diagnostic facilities and blood transfusions. In some developing countries, there are virtually no facilities for diagnosis or management of thalassemia.
Intractability: Thalassemia is not necessarily considered intractable, but it requires lifelong management. The severity of the disease can vary significantly depending on whether a person has a mild, moderate, or severe form. Treatment options, including regular blood transfusions, iron chelation therapy, and potentially bone marrow or stem cell transplants, can help manage symptoms and complications. Advances in medical research and treatment continue to improve the quality of life and prognosis for individuals with thalassemia.
Disease Severity: Thalassemia is a genetic blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. The severity of thalassemia can range from mild to severe depending on the specific type:

1. **Thalassemia Minor (Trait)**: Typically causes no symptoms or mild anemia. People with this form usually live normal lives without needing extensive medical care.
2. **Thalassemia Intermedia**: Causes moderate to severe anemia and can lead to significant health problems. Patients might require occasional blood transfusions and other treatments.
3. **Thalassemia Major (Cooley’s Anemia)**: The most severe form, leading to severe anemia. Patients usually require regular blood transfusions and other medical treatments to manage symptoms and prevent complications.

The severity depends on the specific genetic mutations involved and the patient's response to treatment.
Healthcare Professionals: Disease Ontology ID - DOID:10241
Pathophysiology: Normally, the majority of adult hemoglobin (HbA) is composed of four protein chains, two α and two β-globin chains arranged into a heterotetramer. In thalassemia, patients have defects in either the α or β-globin chain, causing production of abnormal red blood cells.The thalassemias are classified according to which chain of the hemoglobin molecule is affected. In α-thalassemias, production of the α-globin chain is affected, while in β-thalassemia, production of the β-globin chain is affected.The β-globin chains are encoded by a single gene on chromosome 11; α-globin chains are encoded by two closely linked genes on chromosome 16. Thus, in a healthy person with two copies of each chromosome, two loci encode the β chain, and four loci encode the α chain. Deletion of one of the α loci has a high prevalence in people of African or Asian descent, making them more likely to develop α-thalassemia. β-thalassemias are not only common in Africans, but also in Greeks and Turks.
Carrier Status: Carrier status for thalassemia, often referred to as being a thalassemia trait, means that a person has inherited one mutated gene from one parent but typically does not display severe symptoms of the disease. Carriers can pass the mutated gene to their offspring, which may result in thalassemia if the other parent also passes on a thalassemia gene. Carrier status is significant because it helps in genetic counseling and family planning.
Mechanism: Thalassemia is a genetic blood disorder resulting from the reduced production or absence of one of the hemoglobin chains, leading to anemia. The mechanism involves mutations in the genes responsible for hemoglobin production, primarily the HBB gene for beta-globin chains (beta-thalassemia) and the HBA1 and HBA2 genes for alpha-globin chains (alpha-thalassemia).

Molecular Mechanisms:
1. **Beta-Thalassemia**:
- Caused by mutations in the HBB gene on chromosome 11.
- Mutations can lead to reduced (β+) or absent (β0) beta-globin production.
- Common mutations include point mutations, insertions, deletions, and some that affect RNA splicing.
- The imbalance between alpha and beta chains leads to ineffective erythropoiesis and hemolysis.

2. **Alpha-Thalassemia**:
- Caused by deletions or mutations in the HBA1 and HBA2 genes on chromosome 16.
- Genotypic severity ranges from single-gene deletions (silent carrier) to all four-gene deletions leading to Hemoglobin Bart's hydrops fetalis.
- The excess beta chains form unstable tetramers (Hemoglobin H), causing red cell damage and ineffective erythropoiesis.

These disruptions in hemoglobin synthesis result in varying degrees of anemia, depending on the nature and combination of the allelic mutations.
Treatment: Treatment for thalassemia primarily focuses on managing symptoms and reducing complications. Common approaches include:

1. Regular blood transfusions to maintain adequate hemoglobin levels.
2. Chelation therapy to remove excess iron from the body, a side effect of frequent blood transfusions.
3. Folic acid supplements to support red blood cell production.
4. Bone marrow or stem cell transplantation, which can potentially cure the disorder but is only an option for some patients.
5. Gene therapy, an emerging treatment that aims to correct the genetic defects causing the disease.

Management and treatment plans should be customized for each patient based on the severity of their condition and other individual factors.
Compassionate Use Treatment: Thalassemia is a genetic blood disorder that affects the production of hemoglobin. For compassionate use, off-label, or experimental treatments:

1. **Gene Therapy**: Gene therapy has shown promise in preliminary trials for treating certain types of thalassemia, such as beta-thalassemia. It involves modifying the patient's own stem cells to correct the genetic defect causing the disease.

2. **Luspatercept**: This is a relatively new medication that has been granted approval for some cases of thalassemia. Though originally studied for other conditions, its off-label use for thalassemia is being explored to reduce the need for blood transfusions.

3. **Iron Chelators (New Agents)**: While traditional iron chelators like deferoxamine, deferiprone, and deferasirox are standard, new agents are occasionally used off-label in hopes of improving efficacy or reducing side effects.

4. **CRISPR-Cas9**: Experimental treatments using CRISPR-Cas9 technology are being evaluated in clinical trials. This gene-editing approach aims to correct mutations at the DNA level.

5. **Fetal Hemoglobin Inducers**: Drugs such as hydroxyurea, which are used for sickle cell disease, are being researched for their potential off-label use in increasing fetal hemoglobin levels in thalassemia patients.

6. **Bone Marrow/Stem Cell Transplantation**: While this is a more established treatment, newer protocols and less matched donor transplants are experimental options that are being explored to expand the availability of this curative treatment.

These treatments are generally considered when conventional therapies are not effective or feasible, but they require careful consideration and are typically accessed through clinical trials or special programs.
Lifestyle Recommendations: For thalassemia, lifestyle recommendations include:

1. **Regular Medical Follow-ups**: Keep up with scheduled check-ups to monitor the condition and manage complications.
2. **Healthy Diet**: Eat a balanced diet rich in vitamins and minerals, but avoid excess iron unless advised by a healthcare provider.
3. **Avoid Iron Supplements**: Since thalassemia patients can accumulate excess iron, avoid iron supplements unless prescribed.
4. **Exercise**: Engage in moderate exercise to maintain physical health, but avoid strenuous activities that may cause fatigue.
5. **Hydration**: Stay well-hydrated to support overall health.
6. **Vaccinations**: Keep vaccinations up to date to prevent infections, as thalassemia can weaken the immune system.
7. **Genetic Counseling**: If planning to have children, seek genetic counseling to understand the risk of passing the condition on.

These practices help in managing the symptoms and improving the quality of life for individuals with thalassemia.
Medication: Thalassemia is typically managed with regular blood transfusions and iron chelation therapy. Iron chelation helps remove excess iron from the body, which can accumulate due to frequent transfusions. Common iron chelators include:

1. **Deferoxamine (Desferal)** - administered via subcutaneous or intravenous infusion.
2. **Deferasirox (Exjade, Jadenu)** - an oral medication.
3. **Deferiprone (Ferriprox)** - another oral option.

Other treatments may include folic acid supplements, medications to promote red blood cell production, and, in some cases, bone marrow or stem cell transplantation. Regular monitoring and managing complications such as heart and liver issues are also crucial.

Research into gene therapy as a potential cure for thalassemia is ongoing.
Repurposable Drugs: For thalassemia:

Repurposable Drugs:
1. Hydroxyurea: Traditionally used for sickle cell anemia and certain cancers, it can stimulate fetal hemoglobin production.
2. Deferoxamine: Originally used as an iron-chelating agent for iron overload.
3. Erythropoietin: Used in chronic kidney disease, it can help stimulate red blood cell production.

Nanomedicine:
1. Nanoparticle-based gene therapy: Aimed at delivering corrective genes to hematopoietic stem cells.
2. Liposomal drug delivery systems: Enhance the absorption and efficacy of iron chelators.
3. Nanoparticles for controlled drug release: Designed to release drugs more efficiently and reduce toxicity for thalassemia management.
Metabolites: Thalassemia is a blood disorder that affects the body's ability to produce hemoglobin and red blood cells. Metabolites related to thalassemia include:

1. **Iron** - Increased iron levels can occur due to frequent blood transfusions, leading to iron overload.
2. **Bilirubin** - Elevated bilirubin can result from the breakdown of abnormal red blood cells, causing jaundice.
3. **Lactate Dehydrogenase (LDH)** - Elevated LDH levels may indicate the destruction of red blood cells (hemolysis).

Nan refers to "not applicable" in this context, meaning specific details or additional related metabolite information are not provided or necessary here.
Nutraceuticals: Nutraceuticals can play a supportive role in managing thalassemia, particularly in addressing complications like oxidative stress and iron overload. Key nutraceuticals include:

1. **Antioxidants**: Vitamins E and C, selenium, and coenzyme Q10 can help mitigate oxidative damage caused by excess iron.
2. **Omega-3 Fatty Acids**: Found in fish oil, these may reduce inflammation and support heart health.
3. **Curcumin**: Exhibits antioxidant and anti-inflammatory properties, potentially beneficial for overall well-being in thalassemia patients.
4. **Folate and Vitamin B12**: Essential for red blood cell production and reducing anemia severity.

For nanotechnology (nan.), emerging research suggests potential benefits in:

1. **Targeted Drug Delivery**: Nanocarriers can improve the efficacy and reduce the side effects of chelation therapy by specifically targeting iron overload in tissues.
2. **Gene Therapy**: Nanoparticles might be used to deliver gene-editing tools like CRISPR/Cas9 to correct genetic defects causing thalassemia.
3. **Diagnostic Tools**: Nanotechnology-based biosensors could offer rapid and precise detection of thalassemia mutations and track iron levels.

These approaches are still largely experimental but hold promise for the future of thalassemia treatment.
Peptides: Thalassemia is a blood disorder characterized by the body's inability to produce adequate hemoglobin.

- **Peptides**: In the context of thalassemia, peptides could be relevant in therapeutic approaches such as creating peptide-based drugs that might enhance hemoglobin production or function. Currently, research is ongoing to explore how peptide therapies could potentially play a role in managing thalassemia.

- **Nan**: "Nan" may refer to nanotechnology or nanoparticles within the realm of thalassemia treatment and research. Nanotechnology is being explored for targeted drug delivery systems, which could provide more efficient and less invasive treatment options for patients with thalassemia by directly targeting defective cells or improving the efficacy of treatments.