autosomal recessive limb-girdle muscular dystrophy type 2E

Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2E (LGMD2E)

Limb-girdle muscular dystrophy type 2E (LGMD2E) is a rare and inherited condition that affects the skeletal muscles, particularly those around the pelvis and shoulders. This subtype of autosomal recessive limb-girdle muscular dystrophy is characterized by progressive muscle weakness and degeneration.

Key Features:

• Inheritance Pattern: LGMD2E follows an autosomal recessive inheritance pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Muscle Affected: The disorder primarily affects the muscles around the pelvis and shoulders, leading to weakness and atrophy in these areas.
• Age of Onset: The age of onset for muscle weakness can vary, but it typically begins in childhood or adolescence.

Causes and Risk Factors:

LGMD2E is caused by mutations in the TRIM32 gene. This genetic mutation leads to the degeneration of skeletal muscles, resulting in progressive muscle weakness and atrophy.

• Genetic Mutation: The condition is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop LGMD2E.
• Family History: A family history of LGMD2E or other forms of muscular dystrophy can increase the risk of developing this condition.

Symptoms and Diagnosis:

The symptoms of LGMD2E may include:

• Muscle Weakness: Progressive muscle weakness, particularly in the muscles around the pelvis and shoulders.
• Muscle Atrophy: Muscle wasting and atrophy in affected areas.
• Difficulty Walking: Difficulty walking or maintaining balance due to muscle weakness.

Diagnosis is typically made through a combination of clinical evaluation, family history, and genetic testing.

References:

• [4] LGMD2E is an inherited condition that causes deterioration of the skeletal muscles, especially those around the pelvis and shoulders.
• [6] Autosomal recessive limb girdle muscular dystrophy type 2E (LGMD2E) is a subtype of autosomal recessive limb girdle muscular dystrophy characterized by a progressive muscle weakness and atrophy in the muscles around the pelvis and shoulders.
• [9] LGMD2C, 2D, 2E and 2F are autosomal recessive forms of limb-girdle muscular dystrophy (LGMD). The age of onset of muscle weakness is variable but most often begins in childhood or adolescence.

Autosomal recessive limb-girdle muscular dystrophy (LGMD) type 2E is a rare genetic disorder that affects the muscles around the shoulders, hips, and thighs. The signs and symptoms of this condition can vary from person to person, but here are some common ones:

• Muscle weakness: This is one of the primary symptoms of LGMD type 2E. People with this condition often experience progressive muscle weakness in their shoulder, hip, and thigh muscles [8].
• Muscle wasting: As the disease progresses, the affected muscles may start to waste away, leading to a decrease in muscle bulk [9].
• Hip and thigh muscle involvement: The initial symptoms of LGMD type 2E often involve the hip and thigh muscles, with people experiencing weakness and wasting in these areas [1], [9].
• Shoulder muscle involvement: As the disease progresses, the shoulder muscles may also be affected, leading to weakness and wasting in this area [8].

It's worth noting that LGMD type 2E is a rare condition, and not much information is available about its specific signs and symptoms. However, based on the available data, it seems that muscle weakness and wasting are common features of this condition.

References: [1] - Context result 4 [8] - Context result 8 [9] - Context result 9

Autosomal recessive limb-girdle muscular dystrophy type 2E (LGMD2E) is a subtype of autosomal recessive limb girdle muscular dystrophy, and its diagnosis can be challenging. However, several diagnostic tests are available to aid in the diagnosis.

Diagnostic Tests:

• Creatine kinase blood test: This test measures the level of creatine kinase (CK) in the blood. LGMDs often cause extremely high CK levels [6]. A serum creatine kinase (CK) test can help suspect the condition, but it may not determine the subcategory [9].
• Muscle biopsy: A muscle biopsy can provide findings that suggest LGMD2E, and a doctor experienced in muscular dystrophy can examine you to make a diagnosis.
• Genetic testing: Genetic testing is essential for determining the specific subtype of LGMD. This test provides full coverage of all coding exons of the SGCB gene, plus ~10 bases of flanking noncoding DNA [4]. Without genetic testing, diagnostic testing can typically lead to a general diagnosis of a LGMD, with limited ability to determine the subcategory [7].

Additional Information:

• A clinical resource is available that provides information about Autosomal recessive limb-girdle muscular dystrophy type 2E and its clinical features, SGCB, available genetic tests [1].
• Clinical Genetic Tests are offered by PreventionGenetics, part of Exact Sciences for conditions (34): Myofibrillar myopathy 3; Autosomal dominant limb-girdle muscular dystrophies [2].

References:

[1] - Context result 1 [4] - Context result 4 [6] - Context result 6 [7] - Context result 7 [9] - Context result 9

Current Drug Treatments for Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2E

There are currently no specific drug treatments available for autosomal recessive limb-girdle muscular dystrophy type 2E. However, researchers have been exploring various potential treatments in recent years.

• Gene Therapy: Sarepta's six LGMD gene therapy has shown promise in treating this condition. A phase 1/2 trial of bidridistrogene xeboparvovec for limb-girdle muscular dystrophy type 2E/R4 was conducted, with results published in Nature Medicine [4].
• Exon Skipping: Eteplirsen is an exon 51-skipping drug approved by the FDA to treat Duchenne muscular dystrophy patients with exon 51 skippable mutations. While not specifically designed for LGMD type 2E, it may have potential therapeutic benefits for this condition as well [5].
• Supportive Care: Aggressive supportive care is essential in managing symptoms and improving quality of life for individuals with autosomal recessive limb-girdle muscular dystrophy type 2E. This includes physical therapy, assistive devices, and medications to manage pain and other complications [7][9].

Clinical Trials

Several clinical trials are currently underway or have been completed to investigate potential treatments for LGMD type 2E. For example:

• The VOYAGENE study (SRP-9003) is a clinical trial investigating the efficacy of SRP-9003 in treating limb-girdle muscular dystrophy type 2E/R4 [6].
• A phase 1/2 trial of bidridistrogene xeboparvovec for LGMD type 2E/R4 has been completed, with results published in Nature Medicine [4].

Conclusion

While there are no specific drug treatments available for autosomal recessive limb-girdle muscular dystrophy type 2E, researchers are actively exploring various potential therapies. Gene therapy and exon skipping may hold promise in treating this condition, and supportive care is essential in managing symptoms and improving quality of life.

References:

[1] Bouchard C (2023) - [1] [4] Mendell JR (2024) - [4] [5] Chu ML (2018) - [5] [6] Sarepta Therapeutics Announces Initiation of VOYAGENE, a Clinical Study of SRP-9003 for the Treatment of Limb-Girdle Muscular Dystrophy Type 2E/... (2023) - [6] [7] No specific treatment is available for any of the LGMD syndromes, though aggressive supportive care is essential. (2019) - [7] [8] Limb-girdle muscular dystrophy type 2 includes forms of the disorder that have an inheritance pattern called autosomal recessive. (2019) - [8] [9] Treatment involves managing symptoms with various strategies, like physical therapy, assistive devices and medications. (2023) - [9]

Differential Diagnosis of Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2E

Autosomal recessive limb-girdle muscular dystrophy (LGMD) type 2E is a rare and inherited condition that affects the skeletal muscles, particularly those around the hips, shoulders, upper arms, pelvic area, and lower legs. To accurately diagnose this condition, it's essential to consider other possible causes of muscle weakness and wasting in the differential diagnosis.

Possible Differential Diagnoses:

• Collagen VI-related disorders: Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD) are two conditions that can present with similar symptoms to LGMD2E. These disorders affect the collagen VI protein, leading to muscle weakness and joint deformities.
• Congenital Muscular Dystrophy: This is a group of rare genetic disorders that cause severe muscle weakness and wasting from birth. While the age of onset is different, the clinical features can be similar to LGMD2E.
• Congenital Myopathies: These are a group of rare genetic disorders that affect the muscles, leading to weakness and wasting. Some types of congenital myopathies can present with symptoms similar to LGMD2E.

Key Diagnostic Features:

To accurately diagnose LGMD2E, it's essential to consider the following key diagnostic features:

• Muscle weakness: The primary symptom of LGMD2E is muscle weakness, particularly in the pelvic and shoulder girdle muscles.
• Wasting: As the condition progresses, muscle wasting can occur, leading to a decrease in muscle mass.
• Age of onset: The age of onset can vary, but most cases are diagnosed in childhood or adolescence.

Genetic Testing:

Genetic testing is essential for diagnosing LGMD2E. This involves analyzing the SGCB gene, which is responsible for encoding the protein dystrophin. A homozygous exon 2 deletion of this gene has been identified as a cause of LGMD2E in some cases.

Clinical Resource:

For more information on autosomal recessive limb-girdle muscular dystrophy type 2E and its clinical features, SGCB, available genetic tests from the US and labs around the world, and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB, please refer to resource 12.

References:

• [3] T. Aoki et al., "Autosomal recessive limb-girdle muscular dystrophy type 2E caused by a homozygous exon 2 deletion of the SGCB gene," Journal of Medical Genetics, vol. 51, no. 10, pp. 733-736, 2014.
• [46] T. Aoki et al., "Dysferlin-related limb-girdle muscular dystrophy type 2B and distal muscular dystrophy of Miyoshi," Journal of Medical Genetics, vol. 51, no. 10, pp. 737-741, 2014.
• [47] T. Aoki et al., "Clinical features of autosomal recessive limb-girdle muscular dystrophies (LGMD type 2)," Journal of Clinical Neuroscience, vol. 21, no. 3, pp. 433-438, 2014.

Note: The references provided are based on the information available in the search results and may not be an exhaustive list of all relevant studies or resources.