Barth Syndrome
Disease Details
Family Health Simplified
- Description
- Barth syndrome is a rare genetic disorder characterized by an enlarged and weakened heart (cardiomyopathy), muscle weakness, and low levels of certain white blood cells (neutropenia). One-sentence description: Barth syndrome is a rare genetic disorder that affects the heart, muscles, and immune system.
- Type
- Barth syndrome is a rare genetic disorder. It follows an X-linked recessive pattern of inheritance.
- Signs And Symptoms
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Barth syndrome is a rare genetic disorder that primarily affects males and is characterized by various signs and symptoms. These can include:
1. **Cardiomyopathy**: Often dilated or hypertrophic, leading to heart failure.
2. **Neutropenia**: Low levels of neutrophils, a type of white blood cell, which increases the risk of infections.
3. **Skeletal Myopathy**: Muscle weakness and fatigue.
4. **Growth Delay**: Delayed growth during childhood, resulting in shorter stature.
5. **Exercise Intolerance**: Reduced ability to perform physical activities due to muscle weakness and fatigue.
6. **Distinctive Facial Features**: Including a round face, full cheeks, and prominent chin.
7. **Metabolic Abnormalities**: Including 3-methylglutaconic aciduria, which is an elevated level of a specific organic acid in the urine.
The combination and severity of these symptoms can vary widely among individuals with Barth syndrome. - Prognosis
- Barth syndrome is a rare genetic disorder primarily affecting males, characterized by issues such as cardiomyopathy, skeletal muscle weakness, growth delays, and neutropenia. The prognosis varies depending on the severity of symptoms and management of the condition. With improved medical care, early diagnosis, and appropriate treatment, individuals with Barth syndrome can have an improved quality of life and lifespan, though some may still face significant health challenges. Regular monitoring and supportive therapies are essential to manage the symptoms and complications associated with the syndrome.
- Onset
- Barth syndrome typically has an onset in infancy or early childhood. Symptoms can include cardiomyopathy, muscle weakness, growth delay, and neutropenia.
- Prevalence
- Barth syndrome is a rare genetic disorder. The prevalence is not well-defined but it is estimated to affect approximately 1 in 300,000 to 400,000 individuals worldwide.
- Epidemiology
- Being X-linked, Barth syndrome has been predominantly diagnosed in males (as of July 2009: 120+ males), although by 2012 a female case had been reported.The syndrome is believed to be severely under-reported due to the complexity of (early) diagnosis. Reports on its incidence and prevalence in the international literature vary; around 1 in every 454,000 individuals are thought to suffer from Barth Syndrome. Incidence has been estimated at anywhere between 1:140,000 (South West England, South Wales) and 1:300,000
- Intractability
- Barth syndrome is considered intractable in the sense that there is currently no cure for the disease. Management focuses on treating symptoms and improving quality of life through a multidisciplinary approach, but the underlying genetic cause cannot yet be reversed.
- Disease Severity
- Barth syndrome is a rare genetic disorder primarily affecting males. The severity of the disease varies significantly among individuals. It can lead to life-threatening conditions, including cardiomyopathy (weakening of the heart muscle), neutropenia (low levels of neutrophils, a type of white blood cell), muscle weakness, growth delay, and increased risk of infections. Early diagnosis and appropriate management are essential to address the symptoms and improve quality of life.
- Healthcare Professionals
- Disease Ontology ID - DOID:0050476
- Pathophysiology
- Barth syndrome is a rare genetic disorder that primarily affects males. It is caused by mutations in the TAZ gene, which leads to defects in the production of cardiolipin, a lipid that is essential for the normal function of mitochondria. The pathophysiology of Barth syndrome involves a cascade of cellular dysfunctions due to the inadequate production or abnormal composition of cardiolipin. This mitochondrial dysfunction affects high-energy requiring tissues, such as the heart and skeletal muscles, leading to cardiomyopathy, muscle weakness, and increased susceptibility to infections due to neutropenia. Other symptoms can include growth delays and metabolic abnormalities.
- Carrier Status
- Barth syndrome is a rare genetic disorder that primarily affects males. Carrier status refers to individuals who carry one copy of the mutated gene but typically do not show symptoms of the disease. Women can be carriers of Barth syndrome since it is linked to the X chromosome; they may pass the mutated gene to their offspring. Nan (not a number) seems to be out of context here. It is usually used in computing and data processing and does not apply directly to carrier status or genetic conditions.
- Mechanism
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Barth syndrome is a rare genetic disorder primarily affecting males. It is caused by mutations in the TAZ gene, which is also known as G4.5. This gene is responsible for encoding tafazzin, a protein that plays a critical role in the remodeling of cardiolipin, a phospholipid found in the inner mitochondrial membrane.
**Mechanism:**
The primary mechanism involves the defective tafazzin protein due to mutations in the TAZ gene. Cardiolipin is essential for maintaining mitochondrial membrane integrity and function. Reduced or altered cardiolipin impairs mitochondrial function, leading to the various symptoms associated with Barth syndrome, including cardiomyopathy, skeletal muscle weakness, growth delay, neutropenia, and increased levels of organic acids in the urine.
**Molecular Mechanisms:**
1. **Impaired Cardiolipin Remodeling:**
Tafazzin mutations lead to improper remodeling of cardiolipin. Normally, tafazzin facilitates the conversion of immature cardiolipin molecules into their mature, functionally efficient forms.
2. **Mitochondrial Dysfunction:**
Altered cardiolipin affects the inner mitochondrial membrane's stability and its role in energy production. This leads to reduced efficiency of the electron transport chain and impaired ATP synthesis, resulting in decreased energy availability for cells, particularly affecting high-energy-demand tissues such as the heart and muscles.
3. **Increased Reactive Oxygen Species (ROS):**
Dysfunctional mitochondria tend to produce more ROS, which can damage cellular components, including lipids, proteins, and DNA. This oxidative stress further exacerbates mitochondrial dysfunction and contributes to the symptoms of Barth syndrome.
4. **Abnormal Mitochondrial Morphology:**
Due to defective cardiolipin, there is disrupted mitochondrial ultrastructure, leading to enlarged and irregularly shaped mitochondria. This impacts both the function and the mechanical stability of mitochondria within cells.
Collectively, these molecular mechanisms underlie the clinical manifestations of Barth syndrome, making it a complex disease with systemic implications. - Treatment
- Currently, there is no treatment for Barth syndrome, although some of the symptoms can be successfully managed. Clinical trials for possible treatments are ongoing, and preliminary research into AAV9-mediated TAZ gene replacement by the University of Florida has been promising. However, more research and (pre-)clinical testing is needed before the gene therapy is eligible for approval by the FDA as a treatment modality.
- Compassionate Use Treatment
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Barth syndrome is a rare genetic disorder primarily affecting males and characterized by cardiac and skeletal muscle weaknesses, neutropenia, growth delay, and other symptoms. Due to the rarity of the condition, treatment options are limited and often focus on managing symptoms rather than addressing the underlying cause.
**Compassionate Use Treatment**
Compassionate use, also known as expanded access, permits the use of investigational treatments outside of clinical trials for patients with serious conditions who have no other available treatment options. This might include enzyme replacement therapies, experimental drugs specifically targeting mitochondrial function, or therapies aimed at addressing cardiomyopathy or other specific symptoms associated with Barth syndrome.
**Off-Label or Experimental Treatments**
1. **Cardiolipin-Targeted Therapies:** Inducing or stabilizing cardiolipin, the lipid molecule deficient in Barth syndrome, is an area of active research.
2. **Metabolic Modifiers:** Drugs like bezafibrate, originally intended to treat hyperlipidemia, are being studied for their potential to improve mitochondrial function.
3. **Gene Therapy:** There is ongoing research into gene therapy aimed at correcting the underlying genetic defect in the TAZ gene responsible for Barth syndrome.
4. **Carnitine Supplementation:** Some studies suggest that carnitine supplements might help improve muscle function and endurance, though this is still experimental.
5. **Granulocyte Colony-Stimulating Factor (G-CSF):** For patients with significant neutropenia, G-CSF can be used off-label to stimulate the production of white blood cells.
Treatment plans should be tailored to the individual patient and involve a multidisciplinary team to manage the diverse symptoms of Barth syndrome. - Lifestyle Recommendations
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Barth syndrome is a rare genetic disorder that primarily affects males and can lead to a variety of symptoms, including cardiomyopathy, muscle weakness, and low levels of certain white blood cells, among others.
Lifestyle recommendations for individuals with Barth syndrome typically include:
1. **Regular Medical Monitoring:** Frequent check-ups with a multidisciplinary team, including cardiologists, geneticists, and nutritionists, to monitor heart function, growth, and overall health.
2. **Balanced Diet:** A nutritious diet that supports overall health and development. Sometimes, nutritional supplementation may be necessary, especially if the individual has growth delays or specific nutritional deficiencies.
3. **Controlled Physical Activity:** Regular, moderate exercise can be beneficial, but the level and intensity should be tailored to the individual's capacity to prevent overexertion. Cardiac evaluations may guide appropriate activity levels.
4. **Infection Prevention:** Due to immune system involvement, minimizing exposure to infections is crucial. This includes practicing good hygiene, avoiding contact with sick individuals, and staying up-to-date with vaccinations, as recommended by healthcare providers.
5. **Family and Psychological Support:** Support from family, friends, and healthcare professionals is essential for coping with the psychological and emotional challenges associated with the syndrome. Counseling or support groups can also be beneficial.
6. **Education and Advocacy:** Educating teachers, caregivers, and peers about the condition can foster a supportive environment. Advocacy for accommodations in educational settings may be necessary to support learning and development.
These recommendations should be tailored to each individual's specific needs and health status, in consultation with healthcare providers. - Medication
- Barth syndrome is a rare genetic disorder that primarily affects males. It is characterized by muscle weakness, heart problems, growth delay, and other symptoms. There is no specific medication that cures Barth syndrome; treatment typically focuses on managing and alleviating symptoms. This can include nutritional supplementation, medications to manage heart function, and antibiotics to fight infections. Regular follow-ups with a multidisciplinary medical team are essential for monitoring and managing the condition.
- Repurposable Drugs
- Barth Syndrome is a rare genetic disorder primarily affecting males, characterized by cardiomyopathy, muscle weakness, and other systemic issues. There is limited information on repurposable drugs specifically for Barth Syndrome due to its rarity. However, treatment typically focuses on managing the symptoms and complications associated with the condition, such as heart failure medications, antibiotics for infections, and nutritional support. Ongoing research is essential to identify and validate potential repurposable drugs for this condition.
- Metabolites
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Barth syndrome is a rare genetic disorder that primarily affects males. Key metabolites involved in Barth syndrome include:
1. **3-Methylglutaconic Acid**: Elevated levels are a hallmark of Barth syndrome, often detected in urine.
2. **Cardiolipin**: Abnormalities in cardiolipin composition and reduced total cardiolipin levels are characteristic of the disorder.
These metabolic abnormalities are due to mutations in the TAZ gene, which encodes tafazzin, a protein essential for cardiolipin remodeling. - Nutraceuticals
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Nutraceuticals are nutrients or food components that provide medical or health benefits, including the prevention and treatment of disease. For Barth syndrome, a rare genetic disorder affecting mitochondrial function, there is limited evidence on the efficacy of nutraceuticals. While no specific nutraceuticals have been universally recommended for treating Barth syndrome, some patients may benefit from nutritional support aimed at alleviating symptoms and improving quality of life.
Supplements such as coenzyme Q10, omega-3 fatty acids, and certain vitamins and minerals might be considered under medical supervision. These supplements might help with energy production and overall mitochondrial function, but their effectiveness can vary between individuals. Always consult healthcare providers before starting any nutraceutical regimen for Barth syndrome. - Peptides
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Barth syndrome is a genetic disorder primarily affecting males and is characterized by cardiomyopathy, skeletal muscle weakness, and neutropenia, among other symptoms. It is caused by mutations in the TAZ gene, which is involved in the production of tafazzin, a protein important for mitochondrial function.
Peptides: There is ongoing research into peptide-based therapies that might address mitochondrial dysfunction or other aspects of Barth syndrome, but no specific peptide treatments have been established as standard care.
Nanotechnology (nan): Nanotechnology approaches, such as nanoparticle delivery systems, are being explored to deliver therapies more effectively to target tissues, including potentially for diseases like Barth syndrome. However, such approaches are still largely in experimental stages and are not yet a standard treatment for Barth syndrome.