Autosomal Recessive Limb-girdle Muscular Dystrophy Type 2c
Disease Details
Family Health Simplified
- Description
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is a genetic disorder characterized by progressive muscle weakness and wasting, primarily affecting the shoulder and pelvic girdle muscles.
- Type
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is inherited in an autosomal recessive pattern. This means that an individual must receive two copies of the mutated gene, one from each parent, to be affected by the disease.
- Signs And Symptoms
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Signs and symptoms of Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2C (LGMD2C) include:
1. Progressive muscle weakness, primarily affecting the hips, thighs, shoulders, and upper arms.
2. Difficulty walking, frequent falls, and difficulty rising from a sitting or lying position.
3. Waddling gait due to hip muscle weakness.
4. Enlarged calf muscles (pseudohypertrophy).
5. Possible involvement of muscles used for breathing, potentially leading to respiratory issues.
6. Occasionally, mild heart involvement, but significant cardiac issues are rare.
7. Contractures (shortening) of muscles and tendons around joints, leading to reduced mobility.
The onset typically occurs in childhood or adolescence, and the rate of progression can vary widely among individuals. - Prognosis
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) typically has a variable prognosis. This form of muscular dystrophy often leads to progressive muscle weakness, beginning in the muscles of the hips and shoulders. The severity and progression can vary widely among individuals. In more severe cases, patients might experience significant disability and may require the use of a wheelchair in their teenage years or early adulthood. Respiratory and cardiac issues can also arise, which might necessitate medical interventions. Life expectancy can be impacted depending on the severity of the symptoms and associated complications, but with appropriate management and supportive care, many individuals can live into adulthood.
- Onset
- The onset of autosomal recessive limb-girdle muscular dystrophy type 2C typically occurs in early childhood. Symptoms may appear between the ages of 2 and 7 years, though the exact age can vary among individuals.
- Prevalence
- The prevalence of autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is not precisely known but is estimated to be very rare. It varies significantly by population, with higher frequencies reported in specific regions or communities due to founder effects or higher carrier rates. In general, the prevalence is believed to be less than 1 per 100,000 individuals globally.
- Epidemiology
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is a rare genetic disorder. Its estimated prevalence is approximately 1 in 200,000 to 1 in 500,000 in the general population. However, it is more common in certain populations, such as the North African Berber community, due to a higher frequency of the associated genetic mutations.
- Intractability
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is generally considered intractable, meaning there is currently no cure. Management focuses on symptomatic treatment, physical therapy, and supportive care to enhance quality of life and prolong mobility. Research is ongoing to find more effective treatments.
- Disease Severity
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is generally considered to have a severe disease progression. It typically manifests in early childhood with symptoms such as muscle weakness, particularly in the hip and shoulder areas (limb-girdle region). As the disease progresses, affected individuals often experience difficulties with walking and may eventually require the use of a wheelchair. Respiratory complications and cardiomyopathy can also occur, further contributing to the severity of the condition.
- Healthcare Professionals
- Disease Ontology ID - DOID:0110277
- Pathophysiology
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is caused by mutations in the SGCG gene, which codes for the protein γ-sarcoglycan. This protein is part of the sarcoglycan complex within the dystrophin-associated glycoprotein (DAG) complex in muscle cell membranes. Mutations in SGCG lead to a dysfunctional sarcoglycan complex, compromising the integrity and stability of muscle cell membranes, especially during muscle contractions. This results in muscle cell damage, progressive muscle weakness, and wasting, primarily affecting the proximal muscles of the pelvic and shoulder girdles.
- Carrier Status
- For autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C), carrier status typically means that an individual carries one mutated copy of the gene associated with this disorder without showing symptoms. Carriers can pass the mutated gene to their offspring. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit the condition (having two mutated copies), a 50% chance that the child will be a carrier like the parents, and a 25% chance that the child will inherit two normal copies of the gene.
- Mechanism
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Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is caused by mutations in the SGCG gene, which encodes the protein gamma-sarcoglycan. This protein is a critical component of the dystrophin-glycoprotein complex (DGC), which connects the muscle cell cytoskeleton to the extracellular matrix, providing structural stability during muscle contraction.
**Mechanism:**
In LGMD2C, mutations in the SGCG gene lead to a deficiency or dysfunction of gamma-sarcoglycan. This deficiency disrupts the DGC, compromising the integrity of the muscle cell membrane.
**Molecular Mechanisms:**
1. **Protein Misfolding and Degradation:** Mutant gamma-sarcoglycan proteins often misfold and are targeted for degradation by the cellular quality control systems, leading to reduced levels of gamma-sarcoglycan at the muscle cell membrane.
2. **Disrupted DGC Assembly:** The lack of functional gamma-sarcoglycan impedes the proper assembly and stability of the DGC, weakening the connection between the cytoskeleton and the extracellular matrix.
3. **Membrane Instability:** The compromised DGC results in increased fragility of the muscle cell membrane, making it more susceptible to damage during muscle contraction and leading to muscle cell degeneration.
4. **Inflammation and Fibrosis:** The ongoing muscle cell damage triggers inflammatory responses and subsequent fibrotic changes in muscle tissue, contributing to muscle weakness and dysfunction.
These disruptions collectively result in the characteristic muscle weakness and progressive muscle wasting observed in patients with LGMD2C. - Treatment
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For autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C), there is currently no cure. Treatment focuses on symptom management and improving quality of life. This may include:
1. **Physical Therapy**: To maintain mobility and strengthen muscles.
2. **Occupational Therapy**: To assist with daily activities and adaptive strategies.
3. **Medications**: Corticosteroids may be prescribed to slow muscle degeneration.
4. **Orthopedic Devices**: Braces, walkers, or wheelchairs to aid mobility.
5. **Respiratory Care**: Monitoring and supportive therapies for respiratory muscles, including non-invasive ventilation if necessary.
6. **Cardiac Monitoring**: Regular check-ups to monitor heart function, as muscle involvement can impact the heart.
7. **Nutritional Support**: Dietary adjustments to maintain healthy body weight and overall nutrition.
Ongoing research aims to find more effective treatments, including gene therapy and other innovative approaches. Regular consultation with a healthcare provider specializing in neuromuscular disorders is essential for updated and personalized care plans. - Compassionate Use Treatment
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Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is a genetic disorder that affects the muscles, causing progressive weakness and atrophy. For patients with LGMD2C, there are currently no FDA-approved treatments specifically targeting this condition. However, some compassionate use and off-label or experimental treatments may be available:
1. **Corticosteroids**: Although primarily used in Duchenne muscular dystrophy, corticosteroids like prednisone and deflazacort may sometimes be used off-label to manage symptoms and delay progression in LGMD2C.
2. **Gene Therapy**: Experimental gene therapies are being researched to correct the genetic defect responsible for LGMD2C. Clinical trials may be available for eligible patients.
3. **Myostatin Inhibitors**: These are experimental drugs aimed at blocking myostatin, a protein that inhibits muscle growth. They are currently under investigation in clinical trials for various muscular dystrophies, including LGMD2C.
4. **Exon Skipping**: Though still in the experimental stage, exon-skipping therapies that aim to skip the defective exon in the gene may offer potential treatment in the future.
5. **Supportive Treatments**: Physical therapy, occupational therapy, and the use of assistive devices are common supportive measures to improve quality of life.
6. **Nutritional Support**: Proper nutritional support to ensure muscle maintenance and overall health.
Patients seeking access to experimental treatments or clinical trials should consult their healthcare providers or visit clinical trial registries to explore available options. - Lifestyle Recommendations
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For autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C), lifestyle recommendations generally focus on maintaining muscle function, managing symptoms, and optimizing overall health. Here are some strategies:
1. **Physical Therapy and Exercise:**
- Engage in low-impact, regular exercise such as swimming or cycling to maintain muscle strength and flexibility.
- Stretching exercises can help preserve joint mobility.
- Consult with a physical therapist to develop a personalized exercise plan that avoids overexertion.
2. **Assistive Devices:**
- Utilize braces, canes, or wheelchairs as needed to maintain mobility and reduce fall risk.
- Ensure the home environment is adapted to accommodate mobility challenges.
3. **Nutrition:**
- Follow a balanced diet rich in vitamins, minerals, and protein to support overall health.
- Maintain a healthy weight to reduce strain on weakened muscles.
4. **Respiratory Care:**
- Regularly monitor respiratory function as muscular dystrophy can affect breathing.
- Use non-invasive ventilation support if recommended by a healthcare provider.
5. **Cardiac Care:**
- Regular cardiac evaluations may be necessary, as some forms of muscular dystrophy can affect the heart.
- Follow any specific guidelines provided by a cardiologist.
6. **Psychosocial Support:**
- Engage with support groups for emotional and social support.
- Counseling or therapy can be beneficial for coping with the emotional impacts of the condition.
7. **Avoidance of Muscle Overuse:**
- Avoid activities that can cause extreme muscle fatigue or damage.
- Balance activity with adequate rest periods.
8. **Regular Medical Follow-up:**
- Schedule regular check-ups with a neurologist or a specialist in muscular dystrophies.
- Keep track of any changes in symptoms and communicate them to healthcare providers. - Medication
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As of now, there is no specific medication that cures autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD 2C). The management of LGMD 2C focuses on supportive treatments to improve quality of life and manage symptoms. These might include:
1. **Physical Therapy:** To maintain muscle strength and flexibility.
2. **Occupational Therapy:** To assist with daily activities and enhance independence.
3. **Respiratory Support:** In cases of respiratory muscle involvement, non-invasive ventilation may be required.
4. **Cardiac Monitoring:** Regular check-ups to monitor and manage potential heart complications.
5. **Orthopedic Interventions:** Such as braces or surgical procedures to correct skeletal deformities.
Research is ongoing to find potential treatments, including gene therapy and other experimental approaches. - Repurposable Drugs
- There are currently no well-established repurposable drugs specifically for Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2C (LGMD2C). Treatment primarily focuses on symptom management, physical therapy, and supportive care. Research is ongoing to identify potential therapeutic agents, including exploring the repurposing of existing drugs. If new developments occur, they should be closely monitored in scientific literature or through clinical trials.
- Metabolites
- Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2C (LGMD2C) is a genetic disorder caused by mutations in the SGCG gene, which encodes the protein gamma-sarcoglycan. While specific metabolites directly related to LGMD2C have not been extensively documented, muscle tissue in patients with this condition typically exhibits elevated levels of creatine kinase (CK) due to muscle damage. Elevated CK levels serve as a biomarker for muscle disease but are not specific to LGMD2C. Other potential metabolic disturbances may arise secondary to chronic muscle degeneration and impaired muscle metabolism.
- Nutraceuticals
- For autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C), there are currently no specific nutraceuticals proven to treat or cure the disease. Nutraceuticals might be used as part of a broader approach to support overall health and muscle function, but it's crucial to consult with a healthcare provider before starting any new supplement regimen.
- Peptides
- Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is caused by mutations in the SGCG gene, which encodes the protein gamma-sarcoglycan. This protein is part of the dystrophin-glycoprotein complex that helps maintain muscle fiber integrity. Mutations lead to defective gamma-sarcoglycan, compromising muscle cell stability and causing progressive muscle weakness and wasting, particularly in the shoulder and pelvic girdles.