Calpainopathy

Calpainopathy is a genetic muscular dystrophy characterized by progressive muscle weakness and degeneration. It is caused by mutations in the CAPN3 gene, which encodes the enzyme calpain-3. Calpain-3 is a calcium-activated protease that plays a crucial role in muscle fiber maintenance and repair. The absence or malfunction of this enzyme due to genetic mutations leads to the symptoms associated with calpainopathy. This condition is also known as Limb-Girdle Muscular Dystrophy Type 2A (LGMD2A).

Symptoms and Diagnosis

The primary symptoms of calpainopathy include muscle weakness and atrophy, particularly affecting the shoulder and pelvic girdles. The onset of symptoms usually occurs in late childhood or adolescence, but can vary widely among individuals. As the disease progresses, patients may experience difficulty walking, climbing stairs, and performing tasks that require upper body strength. Respiratory and cardiac muscles can also be affected in later stages of the disease.

Diagnosis of calpainopathy is based on clinical examination, family history, and genetic testing to identify mutations in the CAPN3 gene. Muscle biopsy and Creatine Kinase (CK) levels in the blood may also be used to support the diagnosis, as individuals with calpainopathy often have elevated CK levels due to muscle damage.

Treatment and Management

There is currently no cure for calpainopathy, and treatment focuses on managing symptoms and improving quality of life. Physical therapy and occupational therapy can help maintain muscle strength and flexibility, and assistive devices may be used to aid mobility. Regular cardiac and respiratory assessments are important to monitor the involvement of heart and lung muscles and initiate treatment for any complications.

Genetics

Calpainopathy is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease. Carriers of one mutated gene typically do not show symptoms. The CAPN3 gene mutations that cause calpainopathy lead to a deficiency or dysfunction of the calpain-3 protein, disrupting normal muscle maintenance and repair processes.

Research and Future Directions

Research on calpainopathy is focused on understanding the precise role of calpain-3 in muscle function, developing gene therapies to replace or repair the defective gene, and finding ways to enhance muscle repair and regeneration. Clinical trials for potential treatments, including gene therapy and drugs that modulate muscle growth and repair, are ongoing.

See Also

• Muscular Dystrophy
• Genetic Disorders
• Protease
• Gene Therapy