Limb-Girdle Muscular Dystrophy (LGMD) Subtypes

1. LGMD2I (Limb-Girdle Muscular Dystrophy Type 2I - FKRP Deficiency)

LGMD2I is a subtype of limb-girdle muscular dystrophy characterized by muscle weakness and wasting, particularly affecting the muscles around the shoulders and hips. It is caused by mutations in the FKRP gene, leading to a glycosylation defect.

This defect interferes with the proper glycosylation of alpha-dystroglycan, a protein crucial for maintaining muscle cell structure and function. The compromised glycosylation results in muscle degeneration and weakness.

LGMD2I typically presents with a variable age of onset and progression, with symptoms ranging from mild to severe. Physical therapy and supportive care are often recommended to manage symptoms and maintain functional abilities.

2. LGMD2B (Limb-Girdle Muscular Dystrophy Type 2B - DYSF Deficiency)

LGMD2B is another subtype of limb-girdle muscular dystrophy, caused by mutations in the DYSF gene. This gene encodes dysferlin, a protein involved in membrane repair and muscle regeneration.

Deficiencies in dysferlin result in progressive muscle weakness, especially in the shoulder and pelvic girdle muscles. Onset can occur in late adolescence or early adulthood, and the disease typically leads to difficulties in walking, climbing, and other motor functions.

LGMD2B is characterized by muscle inflammation and the presence of muscle fibers with rimmed vacuoles. While there is currently no cure, management involves physical therapy, orthopedic interventions, and respiratory support as needed to improve the quality of life for affected individuals.