Calpainopathy

Calpainopathy is the most common type of autosomal recessive limb-girdle muscular dystrophy (LGMD).

No disease modifying pharmaceuticals have been developed as of 2019, although physical therapy, lifestyle modification, and orthopedic surgery can address symptoms.

[3] Milder forms present with symptoms other than weakness, such as muscle aches, cramps, or exercise intolerance, and people in this group can retain ambulation beyond age 60.

[1] As of 2019, the pathophysiology is largely not understood, although it is increasingly becoming accepted that calcium dysregulation plays a role.

[4] As a protease, it cleaves proteins of the sarcomere and cytoskeleton, designating them to be degraded by proteasomes, a part of muscle remodeling.

[3] Serum creatine kinase, a nonspecific marker of muscle damage, can be elevated early in the disease.

[1] Orthopedic surgery address foot deformities, scoliosis, Achilles tendon contractures, and winged scapula.

[1] Circumstances to avoid include extremes of body weight, bone fractures, and prolonged immobility.

Diagram of calpainopathy pathophysiology, showing calcium dysregulation to play a central role.
Schematic representation of CAPN3 structure. Regions specific to CAPN3 are shown in blue (NS, IS1, and IS2). Regions shared with similar proteins are protease core domains (PC1 and PC2), a calpain-type β-sandwich domain (CBSW), and a penta E-F hand domain (PEF) that binds four calcium ions.
Photomicrograph of muscle affected by calpainopathy. Seen in these views are endomysial fibrosis (black asterisks), central nuclei (black arrows), fiber splitting (yellow triangle), necrosis (black triangles), atrophic fibers (yellow arrows), and increased variation in size and shape. Scale bar: 25 μm