Alpha-sarcoglycanopathy

Alpha-sarcoglycanopathy Alpha-sarcoglycanopathy, also known as Limb-girdle muscular dystrophy type 2D (LGMD2D), is a rare genetic disorder characterized by progressive muscle weakness and wasting, primarily affecting the muscles of the hips and shoulders. This condition is part of a group of disorders known as limb-girdle muscular dystrophies.

Etiology

Alpha-sarcoglycanopathy is caused by mutations in the ]]SGCA]] gene, which encodes the protein alpha-sarcoglycan. This protein is a component of the sarcoglycan complex, which is part of the dystrophin-glycoprotein complex that helps stabilize muscle cell membranes during contraction. Mutations in the SGCA gene lead to a deficiency or dysfunction of alpha-sarcoglycan, resulting in muscle cell damage and progressive muscle weakness.

Clinical Features

The onset of symptoms in alpha-sarcoglycanopathy typically occurs in childhood or adolescence, although the severity and progression can vary widely among individuals. Common symptoms include:

• Progressive weakness of the proximal muscles, particularly those of the pelvic and shoulder girdles.
• Difficulty in climbing stairs, running, or rising from a sitting position.
• Muscle wasting and atrophy.
• Possible involvement of cardiac and respiratory muscles in advanced stages.

Diagnosis

Diagnosis of alpha-sarcoglycanopathy involves a combination of clinical evaluation, genetic testing, and muscle biopsy. Key diagnostic steps include:

• Genetic Testing: Identification of mutations in the SGCA gene confirms the diagnosis.
• Muscle Biopsy: Histological examination may show dystrophic changes, and immunohistochemistry can reveal reduced or absent alpha-sarcoglycan.
• Creatine Kinase Levels: Elevated serum creatine kinase (CK) levels are often observed, indicating muscle damage.

Management

Currently, there is no cure for alpha-sarcoglycanopathy, and treatment is primarily supportive. Management strategies include:

• Physical Therapy: To maintain muscle strength and flexibility.
• Orthopedic Interventions: Such as braces or surgery to address skeletal deformities.
• Cardiac and Respiratory Monitoring: Regular assessments to manage potential complications.

Research and Future Directions

Research into alpha-sarcoglycanopathy is ongoing, with efforts focused on understanding the molecular mechanisms of the disease and developing potential therapies. Gene therapy and other molecular approaches are being explored as potential treatments.

See Also

• Limb-girdle muscular dystrophy
• Muscular dystrophy
• Genetic disorders
• [1] "Alpha-sarcoglycanopathy." Genetics Home Reference. National Institutes of Health.
• [2] "Limb-girdle muscular dystrophy." Muscular Dystrophy Association.

NIH genetic and rare disease info

• NIH info on Alpha-sarcoglycanopathy

Alpha-sarcoglycanopathy is a rare disease.