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Limb Girdle Muscular Dystrophy type 2L or R12 is a rare genetic disorder that causes progressive muscle weakness. It primarily affects the muscles around the shoulders, upper arms, and thighs, known as the limb girdle muscles. These muscles play a key role in basic activities like walking, lifting, and standing. As the disease progresses, healthy muscle tissue degenerates and is replaced by non-functional tissue, such as fat and scar tissue. This degeneration impairs mobility and muscle strength. The condition is caused by mutations in the ANO5 gene, which is responsible for producing a protein that is vital to muscle cell function and repair.

What is LGMD2L?

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These mutations affect the function of the ANO5 protein, which is essential for the repair and maintenance of muscle cells. When the protein is defective or absent, muscle cells cannot repair minor injuries effectively, leading to muscle degeneration. Over time, this results in progressive weakness and the loss of muscle tissue, particularly in the shoulder, hip, and upper arm muscles.

Because LGMD2L is rare and not widely tested for, most people don't realize they have it until their symptoms become severe.

LGMD2L is an autosomal recessive condition, meaning a person must inherit two mutated copies of the ANO5 gene—one from each parent—to develop the disease. If both parents are carriers of the mutated gene, there is a 25% chance with each pregnancy that the child will inherit two mutated copies and develop LGMD2L.

What causes LGMD2L?

Muscle pain is also common. The disease does not typically affect facial or eye muscles, but rarely patients may develop lung or heart complications in later stages. Despite these challenges, people with LGMD2L usually maintain some degree of independence, especially in the earlier stages of the disease.

The gradual loss of muscle function isn't just physical—it's emotional. For those living with LGMD2L, the disease affects daily life and the things we take for granted.

LGMD2L often begins to show symptoms in the 30s, but the age of onset can vary. As the disease progresses, individuals may experience difficulty with activities like standing up from a seated position, climbing stairs, or lifting their arms. In the later stages, these difficulties become more pronounced, and patients may need mobility aids such as canes, leg braces, or wheelchairs to assist with movement. The weakness typically affects the proximal muscles, which are located near the body’s core, such as those in the shoulders, upper arms, and thighs. However, while LGMD2L can cause significant disability, it does not typically shorten life expectancy.

How does LGMD2L affect the body?

Understanding the exact role of the ANO5 protein is critical for developing new therapies. Researchers are exploring how gene therapy or other innovative treatments could correct or replace the ANO5 gene, offering a way to restore proper muscle cell function and halt disease progression.

The ANO5 gene encodes a protein that mostly sits on the edge of the muscle, the membrane, but its function is not fully understood. ANO5 can move lipid molecules around and this may play a role in attracting and organizing the proteins required to repair the muscle when it is injured. It may also help move electrically charged atoms in and out of the muscle cell, but it is not known how this might affect muscle repair. Whatever its function, when the ANO5 gene is mutated the protein either does not work properly or is completely absent. This disruption makes it difficult for muscle cells to repair themselves after minor injuries, leading to muscle cell breakdown and degeneration. As a result, muscle weakness gradually worsens over time.

What is the role of the ANO5 gene?

By exploring the repair process of muscle cells in the lab, scientists aim to uncover why muscles without ANO5 cannot regenerate effectively after injury. This research is crucial for identifying potential therapies that could preserve muscle function and slow disease progression. Ultimately, these insights will guide the development of treatments aimed at restoring the natural repair mechanisms that are lost in individuals with LGMD2L.

Every step forward in research brings us closer to a solution, and your participation could be the key that unlocks the cure for LGMD2L.

Understanding how the absence of ANO5 causes muscle damage is key to advancing treatments for LGMD2L. Pathophysiology research focuses on the mechanisms by which this lack of ANO5 disrupts muscle repair and function. Researchers are studying how muscle cells behave with and without ANO5 to determine how the gene affects muscle function and repair.

Why is pathophysiology research important for LGMD2L?

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Help shape the future of LGMD2L research.

By joining the LGMD2L Registry, you’ll provide valuable data that supports life-changing breakthroughs.

About LGMD2L

Phone: (224) 392-5420

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By joining the LGMD2L Registry, you can contribute to this vital research and help us make a lasting impact.

As you live with LGMD2L, it’s important to remember that you are not alone. There is a growing network of support, including researchers, healthcare professionals, and other patients, working together to better understand the condition and find solutions. With continued research and your participation, we can move closer to improving the lives of those affected by LGMD2L. As well as our public social media accounts linked at the bottom of this page, we run a private Facebook group for patients and caregivers to share their experiences with others affected.

While the progression of LGMD2L is unique to each individual, the condition typically advances slowly. Many people with LGMD2L experience a gradual decline in muscle strength, often beginning in their 30s, but symptoms develop at different rates. The slower progression can bring some comfort to those newly diagnosed, as it allows more time for adjustment and coping. Additionally, the ongoing research and efforts by the LGMD2L Foundation are focused on finding effective treatments that can make a difference during your lifetime, offering hope that progress in research can lead to improved outcomes and potentially transformative therapies.

Living with LGMD2L

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