GeneHealth - Your precision medicine

Autosomal Recessive Limb-girdle Muscular Dystrophy Type 2i

Disease Details

Family Health Simplified

Buy Membership

Description: Autosomal recessive limb-girdle muscular dystrophy type 2I is a genetic disorder characterized by progressive muscle weakness and wasting, primarily affecting the muscles around the hips and shoulders.
Type: Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is transmitted in an autosomal recessive manner.
Signs And Symptoms: For autosomal recessive limb-girdle muscular dystrophy type 2I (LGMDR9 or LGMD2I), the signs and symptoms typically include:

- Progressive muscle weakness, particularly in the hip and shoulder areas (limb-girdle muscles)
- Difficulty walking or running, often resulting in a waddling gait
- Trouble climbing stairs or rising from a seated position
- Muscle pain and cramps
- Enlarged calf muscles (pseudohypertrophy)
- Respiratory complications in advanced stages due to weakness of respiratory muscles
- Cardiomyopathy, which may involve heart muscle weakness and conduction defects

The onset and progression of symptoms can vary widely among individuals.
Prognosis: Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) generally has a variable prognosis, but it typically involves a progressive decline in muscle strength and function. Some patients may maintain mobility for many years, while others may require mobility aids or become wheelchair-dependent more rapidly. Life expectancy can be near normal for some, but respiratory complications or cardiac involvement may impact survival in more severe cases. The progression and severity can vary significantly between individuals.
Onset: The onset of autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) typically occurs in late childhood to early adulthood. Symptoms, however, can vary significantly among individuals.
Prevalence: The prevalence of autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is not precisely known, but it is considered a rare disorder. In certain populations, the prevalence is estimated to be less than 1 in 100,000 individuals.
Epidemiology: Epidemiology refers to the study of the distribution and determinants of health-related states and events in specified populations. For autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I):

- **Prevalence**: LGMD2I is considered a rare disorder. Exact prevalence rates can vary by region, but it generally affects fewer people globally compared to other forms of muscular dystrophy.

- **Geographic Distribution**: This condition has been reported worldwide, though specific regional prevalence can vary due to genetic factors and population differences.

- **Age of Onset**: Symptoms usually begin in late childhood to early adulthood, but there can be significant variability.

- **Gender Distribution**: As an autosomal recessive disorder, it affects males and females equally.

- **Risk Factors**: The primary risk factor is inheriting two mutated copies of the FKRP gene, one from each parent. Parents are usually asymptomatic carriers of the mutation.
Intractability: Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is generally considered a chronic and currently intractable condition. This means that, as of now, there is no cure, and treatment primarily focuses on managing symptoms and improving quality of life. Research is ongoing to develop potential therapies, but effective treatment options to reverse or halt disease progression are not yet available.
Disease Severity: For autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I), the disease severity can vary widely among affected individuals. Generally, it is a progressive muscle disease characterized by weakness and wasting of the muscles around the hips and shoulders. Severity can range from mild to severe:

- **Mild cases:** Individuals might experience slower progression of muscle weakness and retain the ability to walk well into adulthood.
- **Moderate cases:** Progressive weakness may lead to the loss of ambulation in the teenage or early adult years, requiring aids such as braces or wheelchairs.
- **Severe cases:** Rapid progression of muscle weakness might result in loss of ambulation in childhood and potential involvement of respiratory and cardiac muscles, leading to complications that can reduce lifespan.

There is no complete cure, but supportive treatments can improve quality of life and manage symptoms.
Healthcare Professionals: Disease Ontology ID - DOID:0110299
Pathophysiology: **Pathophysiology:**

Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the FKRP (fukutin-related protein) gene. FKRP is involved in the glycosylation process of alpha-dystroglycan, an important protein for maintaining the integrity of muscle cell membranes. Mutations in FKRP lead to defective glycosylation of alpha-dystroglycan, which impairs its ability to bind to other extracellular matrix proteins. This disruption weakens the structural stability of muscle cells, making them more susceptible to damage during muscle contractions. Over time, this leads to muscle fiber degeneration and progressive muscle weakness, particularly in the hip and shoulder areas, characteristic of limb-girdle muscular dystrophies.
Carrier Status: Carriers of autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) have one mutated copy of the gene and one normal copy. Carriers typically do not show symptoms of the disease but 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 two mutated genes and have the condition, a 50% chance that the child will be a carrier, and a 25% chance that the child will inherit two normal genes.
Mechanism: Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is primarily caused by mutations in the FKRP (fukutin-related protein) gene. The mechanism involves a defective glycosylation of α-dystroglycan, a key protein integral to the stability and function of muscle fibers.

**Molecular Mechanisms:**
1. **Genetic Mutation**: Mutations in the FKRP gene impair the enzyme's ability to add sugar molecules (glycosylation) to α-dystroglycan.
2. **α-Dystroglycan Hypoglycosylation**: Proper glycosylation is crucial for α-dystroglycan's function. Without it, the protein cannot effectively interact with the extracellular matrix.
3. **Muscle Fiber Degeneration**: The lack of functional α-dystroglycan leads to compromised muscle membrane stability, making muscle fibers more susceptible to damage.
4. **Progressive Muscle Weakness**: Over time, the cumulative damage to muscle fibers results in progressive muscle weakness and degeneration, particularly affecting the limb and girdle muscles.

These molecular dysfunctions collectively contribute to the pathophysiology of LGMD2I.
Treatment: For autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I), treatment primarily focuses on managing symptoms and improving quality of life, as there is currently no cure. Management strategies may include:

1. **Physical Therapy**: Customized exercises to maintain muscle strength and flexibility.
2. **Occupational Therapy**: Assistance with daily living activities and adaptive devices.
3. **Respiratory Care**: Monitoring and support for respiratory functions, possibly including non-invasive ventilation.
4. **Cardiac Care**: Regular cardiac evaluations and management of potential heart complications.
5. **Medications**: Corticosteroids in some cases to potentially slow disease progression.
6. **Orthopedic Interventions**: Braces or surgical procedures to address skeletal deformities.
7. **Nutritional Support**: Dietary adjustments to support overall health and muscle function.

Research on gene therapy and other novel treatments is ongoing, but these approaches are still in experimental stages. Regular follow-ups with a healthcare team experienced in muscular dystrophies are essential.
Compassionate Use Treatment: Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is a genetic disorder characterized by progressive muscle weakness, particularly affecting the hips and shoulders. For compassionate use, off-label, or experimental treatments, the following avenues may be explored:

1. **Gene Therapy:** Experimental trials are underway to deliver functional copies of the affected FKRP gene to muscle cells.

2. **Readthrough Compounds:** Pharmacological agents that promote the readthrough of premature stop codons, potentially restoring some functional protein production, are in experimental stages.

3. **Exon Skipping:** This technique aims to skip over faulty exons in the FKRP gene, with the potential to minimize disease severity. While primarily tested in other muscular dystrophies, the approach is under consideration for LGMD2I.

4. **Steroids and Anti-inflammatory Drugs:** While not curative, corticosteroids or other anti-inflammatory medications may be used off-label to improve muscle strength and reduce inflammation.

5. **Myostatin Inhibitors:** These experimental drugs aim to inhibit myostatin, a negative regulator of muscle growth, potentially increasing muscle mass and strength.

6. **Cell Therapy:** Research into stem cell or other cell-based therapies is ongoing, with the goal of repairing or regenerating damaged muscles.

Patients should consult healthcare professionals to discuss these options, potential enrollment in clinical trials, and the availability of compassionate use programs for experimental treatments.
Lifestyle Recommendations: Individuals with autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) can adopt certain lifestyle recommendations to manage their condition better and maintain quality of life:

1. **Regular Physical Therapy**: Engage in low-impact exercises to maintain muscle strength, flexibility, and joint mobility. Physical therapy can help in preventing contractures and worsening muscle atrophy.

2. **Energy Conservation**: Practice techniques to conserve energy, such as using assistive devices, taking frequent breaks, and prioritizing activities to avoid fatigue.

3. **Healthy Diet**: Follow a balanced diet to support overall health and nutritional needs. Maintaining an appropriate weight can reduce stress on weakened muscles.

4. **Cardiac Monitoring**: Regular check-ups with a cardiologist are advised, as LGMD2I can sometimes affect the heart. Adhering to prescribed treatments and lifestyle adjustments is essential.

5. **Respiratory Care**: Monitor respiratory functions regularly. Breathing exercises, using devices like ventilators if necessary, and consulting with a pulmonologist can help manage respiratory complications.

6. **Safety Adaptations**: Modify living spaces to prevent falls and injuries, such as installing grab bars, non-slip mats, and ramps if needed.

7. **Support Networks**: Join support groups and connect with others dealing with similar conditions for emotional support and shared experiences.

8. **Regular Medical Follow-ups**: Keep consistent appointments with healthcare providers to monitor the progression of the disease and adjust treatments as necessary.

These recommendations can help manage symptoms and improve the quality of life for individuals with LGMD2I.
Medication: There is currently no medication that cures autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I). Treatment is mainly supportive and focuses on managing symptoms and improving quality of life. This can include physical therapy, occupational therapy, respiratory support, and cardiac care. Research is ongoing to find effective treatments.
Repurposable Drugs: For Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I), there is ongoing research into repurposable drugs aimed at managing the symptoms or slowing the progression of the disease. While there is no definitive cure, some drugs under investigation include:

1. **Ataluren**: Originally used for Duchenne muscular dystrophy, it targets nonsense mutations and may have applications in similar dystrophies.
2. **Losartan**: Typically used for hypertension, it has potential benefits in managing fibrosis and inflammation in muscular dystrophies.
3. **Metformin**: Commonly used for diabetes, it is being explored for its muscle regenerative properties and possible benefits in muscle dystrophies.

These drugs are still under various stages of research, and their use should be guided by clinical trials and professional medical advice.
Metabolites: Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I) is caused by mutations in the FKRP gene. Metabolites specifically associated with this disorder are not well-characterized. However, research in muscular dystrophies often examines muscle tissue samples for biomarkers such as creatine kinase, which is typically elevated due to muscle breakdown. Additionally, metabolic profiling in affected individuals may reveal disruptions in muscle energy metabolism, but specific metabolite alterations for LGMD2I are still under investigation.
Nutraceuticals: For autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I), there is limited evidence regarding the effectiveness of nutraceuticals. While some supplements like creatine, coenzyme Q10, and antioxidants may be considered to support general muscle health, their specific benefit for LGMD2I is not well-established. It is crucial to consult a healthcare professional before starting any nutraceutical regimen.

If "nan" refers to "nanotechnology," research is ongoing in the field of nanomedicine to develop targeted therapies for muscular dystrophies, including LGMD2I. However, these technologies are still largely in the experimental stage and not yet available as standard treatments.
Peptides: For autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I), particularly linked to mutations in the FKRP gene, advancements in peptide-based therapies are under investigation. These therapies often focus on using synthetic peptides to either correct the defective protein function or to modulate pathways affected by the mutation. Nanotechnology is being explored to improve the delivery of these peptide-based therapies, aiming to enhance stability, targeting, and uptake by muscle cells. Additionally, nanoparticles may facilitate the delivery of genetic material or drugs to affected tissues, potentially offering new avenues for treatment. Research is ongoing to optimize these approaches for clinical use.