POMGNT1-related limb-girdle muscular dystrophy R15

POMGNT1-related limb-girdle muscular dystrophy R15 (LGMD R15, formerly known as LGMD2O) is a rare autosomal recessive muscular dystrophy caused by biallelic pathogenic variants in the POMGNT1 gene. This gene encodes protein O-linked mannose N-acetylglucosaminyltransferase 1, an enzyme essential for the proper glycosylation of alpha-dystroglycan, a key protein that links the muscle cell cytoskeleton to the extracellular matrix. LGMD R15 belongs to the group of dystroglycanopathies — disorders caused by defective glycosylation of alpha-dystroglycan. The disease primarily affects the skeletal muscular system, with progressive weakness predominantly involving the proximal muscles of the limb girdles (shoulders and hips). Patients typically present with difficulty climbing stairs, rising from a seated position, and raising their arms. Serum creatine kinase (CK) levels are usually elevated. The severity of LGMD R15 can vary considerably; some patients have a relatively mild course with preserved ambulation into adulthood, while others may experience more significant disability. Cognitive involvement, including mild intellectual disability, and eye abnormalities (such as myopia) have been reported in some cases, reflecting the broader phenotypic spectrum of POMGNT1-related dystroglycanopathies, which can range from the severe Walker-Warburg syndrome and muscle-eye-brain disease to milder limb-girdle presentations. There is currently no cure or disease-specific treatment for LGMD R15. Management is supportive and multidisciplinary, including physical therapy to maintain mobility and prevent contractures, respiratory monitoring, cardiac surveillance, and orthopedic interventions as needed. Genetic counseling is recommended for affected families. Research into gene therapy and other molecular approaches for dystroglycanopathies is ongoing but remains in early stages.

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