Muscular dystrophy limb girdle type 2A, Erb type

Muscular Dystrophy, Limb-Girdle, Type 2A, Erb Type (LGMD2A), also known as Calpainopathy, is a form of Limb-Girdle Muscular Dystrophy (LGMD) characterized by progressive muscle weakness and atrophy primarily affecting the shoulder and pelvic girdles. The condition is named after Wilhelm Heinrich Erb, a pioneer in the field of neurology who first described the disease spectrum. LGMD2A is caused by mutations in the CAPN3 gene, which encodes the muscle-specific enzyme calpain-3. This enzyme plays a crucial role in muscle fiber maintenance and repair. The autosomal recessive inheritance pattern of LGMD2A means that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the condition.

Symptoms and Diagnosis[edit | edit source]

The onset of symptoms typically occurs in late childhood to early adulthood, but can vary widely. Initial symptoms often include difficulty running, climbing stairs, and rising from a seated position. As the disease progresses, affected individuals may experience muscle wasting (atrophy), leading to increased disability. The rate of progression can vary; some individuals may lose the ability to walk in later life, while others maintain mobility with assistance.

Diagnosis of LGMD2A is based on clinical examination, family history, and genetic testing to identify mutations in the CAPN3 gene. Muscle biopsy and enzyme assays may also be used to support the diagnosis by demonstrating reduced or absent calpain-3 activity.

Treatment and Management[edit | edit source]

There is currently no cure for LGMD2A, 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 necessary as the disease progresses. Regular cardiac and respiratory assessments are important, as individuals with LGMD2A may develop complications affecting the heart and lungs.

Genetics[edit | edit source]

The CAPN3 gene provides instructions for producing the enzyme calpain-3. Mutations in this gene lead to reduced activity or stability of calpain-3, which is essential for muscle fiber repair and regeneration. The autosomal recessive inheritance pattern of LGMD2A requires both parents to carry one copy of the mutated gene, although they typically do not show symptoms of the disease themselves.

Research[edit | edit source]

Research efforts are focused on understanding the molecular mechanisms underlying LGMD2A and developing effective treatments. Gene therapy, aimed at delivering functional copies of the CAPN3 gene to muscle cells, and therapies targeting the pathways affected by calpain-3 deficiency are areas of active investigation.