autosomal recessive limb-girdle muscular dystrophy type 2A

Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2A (LGMD2A)

Autosomal recessive limb-girdle muscular dystrophy type 2A, also known as Calpainopathy, is a rare genetic disorder that affects the muscles around the pelvis and shoulders. This condition is characterized by progressive weakness and wasting of the proximal limb-girdle muscles [1].

Causes and Inheritance

LGMD2A is caused by mutations in the calpain 3 (CAPN3) gene, which is inherited in an autosomal recessive pattern [6]. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Symptoms and Age at Onset

The age at onset of muscle weakness ranges from two to adulthood, with most cases presenting in childhood or adolescence [8]. The symptoms typically start with difficulty walking due to weakness and wasting of the proximal muscles. As the disease progresses, other muscles may be affected, leading to further mobility issues.

Key Features

• Symmetric and progressive weakness: Calpainopathy is characterized by symmetric and progressive weakness of proximal limb-girdle muscles.
• Autosomal recessive inheritance: The condition is inherited in an autosomal recessive pattern, meaning a person must inherit two copies of the mutated gene to develop the condition.
• Difficulty walking: The age at onset varies, but most cases present with difficulty walking due to weakness and wasting of the proximal muscles.

References

[1] Context 1: Limb girdle muscular dystrophy 2A (LGMD2A) also known as Calpainopathy is an autosomal recessive form of limb girdle muscular dystrophy (LGMD).

[6] by CH Wang · 2015 · Cited by 15 — The autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 (CAPN3) gene, and it is characterized by ...

[8] Autosomal recessive limb-girdle muscular dystrophy-1 affects primarily the proximal muscles, resulting in difficulty walking. The age at onset varies, but most ...

Autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) is a genetic disorder that affects the muscles around the shoulders and hips. The main symptoms of LGMD2A are:

• Progressive muscle weakness: Muscle weakness starts in childhood or young adulthood, affecting the proximal muscles (those closest to the body core).
• Muscle atrophy: As the disease progresses, muscles may shrink and become weaker.
• Exercise-induced myalgia: Some people with LGMD2A experience muscle pain during exercise, particularly in the thighs and hips.

In addition to these symptoms, some individuals with LGMD2A may also experience:

• Cardiac arrhythmia: Abnormal heart rhythms have been reported in some cases of LGMD2A.
• Muscle hypertrophy: In some cases, muscles may become larger than normal (hypertrophic).

It's essential to note that the age of onset and severity of symptoms can vary widely among individuals with LGMD2A. The disease is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations.

References:

• [10] describes LGMD2A as one of the most common forms of LGMD, with a variable age of onset ranging from 8 to 15 years.
• [12] reports symptoms such as exercise-induced myalgia and cardiac arrhythmia in individuals with LGMD2A.
• [5] mentions muscle weakness and atrophy as progressive features of LGMDs, which applies to LGMD2A.

Autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) is a genetic disorder that can be diagnosed through various diagnostic tests.

Clinical Genetic Test: A clinical genetic test, such as the one offered by Bioarray, can be used to diagnose LGMD2A. This test involves examining a blood sample for DNA mutations in the CAPN3 gene, which is responsible for the condition [5][6].

Creatine Kinase Testing: Creatine kinase testing is another diagnostic tool that can aid in the diagnosis of LGMD2A. High levels of creatine kinase are often found in individuals with this condition [7].

Muscle Biopsy and Genetic Testing: A muscle biopsy followed by genetic testing can also be used to diagnose LGMD2A. This involves examining a sample of muscle tissue for signs of damage and then conducting DNA testing to confirm the diagnosis [8][9].

Biochemical Protein Testing: Biochemical protein testing performed on muscle biopsies can also help in diagnosing specific subtypes of LGMD, including LGMD2A [10].

It's worth noting that a combination of clinical assessment, specialized muscle immunoanalysis, and genetic testing is often used to diagnose LGMD2A, especially in informative families where there is a known family history of the condition [9].

Current Status of Drug Treatment for Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2A

There is no specific medication used for the treatment of autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) [4]. However, various strategies are employed to manage symptoms and improve quality of life.

• Gene Therapy Strategies: Researchers have explored gene therapy as a potential approach to reverse the CAPN3 defect responsible for LGMD2A. This involves administering an adeno-associated virus (AAV)-associated CAPN3 gene to systemically or locally administer the gene [2].
• Other Potential Treatments: Studies have investigated other potential treatments, such as stem-cell transplantation, exon skipping, and gene editing technologies like CRISPR/Cas9 [3]. However, these approaches are still in the early stages of development.
• Supportive Care: Aggressive supportive care is essential for managing symptoms and improving quality of life. This may include physical therapy, assistive devices, and medications to alleviate muscle weakness and other symptoms [7].

Current Research and Development

A cell therapy candidate has been proposed for LGMD2A, which is currently in preclinical studies [9]. Additionally, research on gene therapy strategies continues to advance, with a focus on developing effective treatments for this condition.

References:

[1] To date there are no specific treatments for LGMD2A, however careful management of the symptoms of the condition can improve a person's quality of life. Keeping ...

[2] by İO Şahin · 2021 · Cited by 6 — One of the gene therapy strategies designed to reverse the CAPN3 defect is to systemically or locally (intramuscularly) administer AAV-associated CAPN3 gene ...

[3] by C Bouchard · 2023 · Cited by 10 — In the last decade, multiple other potential treatments were developed and studied, such as stem-cell transplantation, exon skipping, gene ...

[4] Jul 9, 2021 — Medication Summary. No medication is used for the specific treatment of limb-girdle muscular dystrophy.

[5] Orphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the ...

[6] Sep 1, 2019 — Limb-girdle muscular dystrophy type 2 includes forms of the disorder that have an inheritance pattern called autosomal recessive .

[7] Dec 12, 2023 — Treatment involves managing symptoms with various strategies, like physical therapy, assistive devices and medications.

[8] Aug 15, 2019 — No specific treatment is available for any of the LGMD syndromes, though aggressive supportive care is essential.

[9] The candidate is a cell therapy for limb-girdle muscular dystrophy type 2a (LGMD2A), the most common type of LGMD. While it's still in preclinical studies, ...

[10] by V Straub · 2008 · Cited by 25 — Martin, et al. Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A. Mol Ther, 13 (2006) ...

The differential diagnosis for autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A), also known as Calpainopathy, includes several conditions that can present with similar symptoms. Some of these conditions are:

• Collagen VI related disorders: Bethlem myopathy and Ullrich CMD
• Congenital Muscular Dystrophy
• Congenital Myopathies

These conditions can be distinguished from LGMD2A through genetic and protein analysis [5]. It's essential to note that the precise differential diagnosis of limb girdle muscular dystrophies is crucial for genetic counseling, prognostic orientation, cardiac and respiratory management, and overall patient care [10].

In particular, the differential diagnosis of LGMD includes facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, congenital muscular dystrophy, and other conditions that can present with similar symptoms to LGMD2A [6]. However, these disorders can now be distinguished by genetic and protein analysis [7].

It's also worth noting that the LGMD R group, which includes autosomal recessive forms of LGMD like LGMD2A, can be distinguished from other forms of LGMD through inheritance pattern analysis. Specifically, LGMD2A is inherited in an autosomal recessive manner, meaning that a genetic mutation must be present on both copies of the gene for the condition to manifest [9].

References: [5] Aug 15, 2019 — Differential Diagnoses · Collagen VI related disorders. Bethlem myopathy and Ullrich CMD · Congenital Muscular Dystrophy · Congenital Myopathies. [6] The differential diagnosis of LGMD includes facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, congenital muscular dystrophy, ... [7] Oct 1, 2019 — These disorders can now be distinguished by genetic and protein analysis. The various forms of LGMD may be inherited as autosomal dominant or ... [8] Called LGMD1 and LGMD2, these two groups are classified by the respective inheritance patterns: autosomal dominant and autosomal recessive. [9] Dec 12, 2023 — The LGMD R group: These LGMDs happen due to autosomal recessive inheritance patterns. This means you've inherited a genetic mutation that causes ... [10] by A Cotta · 2014 · Cited by 46 — The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory ...