Calpain-3-related limb-girdle muscular dystrophy R1

Calpain-3-related limb-girdle muscular dystrophy R1 (LGMDR1), formerly known as LGMD2A, is an autosomal recessive muscular dystrophy caused by pathogenic variants in the CAPN3 gene, which encodes the muscle-specific protease calpain-3. It is the most common form of limb-girdle muscular dystrophy worldwide. The disease primarily affects the skeletal muscular system, leading to progressive weakness and wasting of the proximal muscles of the shoulders (shoulder girdle) and hips (pelvic girdle). Early symptoms typically include difficulty running, climbing stairs, and rising from the floor, often beginning in childhood or adolescence. The posterior thigh and hip adductor muscles are characteristically affected early, and scapular winging is a common finding. Contractures of the Achilles tendons, elbows, and spine may develop. Cardiac and respiratory muscles are generally spared or only mildly affected, though respiratory function should be monitored as the disease progresses. The rate of disease progression is variable but generally slow, with many individuals remaining ambulatory into their third or fourth decade of life, though some may require wheelchair use earlier. Serum creatine kinase (CK) levels are typically markedly elevated, often 10 to 50 times the upper limit of normal, even in early stages. Muscle biopsy shows dystrophic changes, and calpain-3 protein may be reduced or absent on Western blot analysis. Genetic testing of the CAPN3 gene confirms the diagnosis. There is currently no cure or disease-specific treatment for LGMDR1. Management is supportive and includes physical therapy to maintain mobility and prevent contractures, orthopedic interventions as needed, respiratory monitoring, and psychosocial support. Research into potential gene therapies and other molecular approaches is ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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