autosomal recessive limb-girdle muscular dystrophy type 2R1

Autosomal recessive limb-girdle muscular dystrophy type 2R1 is a very rare inherited condition that primarily affects the proximal muscles responsible for movement and ambulation. It is caused by pathogenic variants in the POGLUT1 gene, which encodes the enzyme protein O-glucosyltransferase 1, essential for normal muscle tissue maintenance. Affected individuals typically experience progressive muscle weakness, leading to difficulties in walking and other motor functions. This condition is very rare, affecting fewer than one in a million people.

The clinical presentation is marked by characteristic features such as limb-girdle muscular dystrophy, scapular winging, and fatty replacement of skeletal muscle, all of which are always present. Early in the disease, affected individuals develop proximal lower limb muscle weakness and skeletal muscle atrophy, which can lead to challenges in walking and mobility. As the condition progresses, some individuals may experience reduced forced vital capacity, restrictive ventilatory defects, and even loss of ambulation, while a subset show elevated circulating creatine kinase levels. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the POGLUT1 gene, which impair the function of protein O-glucosyltransferase 1, a key enzyme in muscle tissue maintenance. It is inherited in an autosomal recessive pattern, meaning that an affected individual inherits two mutated copies of the gene, one from each parent. This condition is more common when parents share a common ancestor, as the probability that both carry the same rare variant is increased. Genetic counseling is recommended to help families understand recurrence risks and explore family planning options.

Currently, management focuses on supportive care and symptom management. Treatment is individualized and typically involves a multidisciplinary team that may include physical therapists, occupational therapists, and respiratory specialists to help maintain mobility and manage complications. Patients should discuss treatment options with their healthcare team to determine which supportive interventions may be most beneficial, and genetic counseling is encouraged to better understand the inheritance pattern and implications for the family.

The long-term outlook for individuals with autosomal recessive limb-girdle muscular dystrophy type 2R1 is variable and depends on factors such as the severity of muscle weakness, age at diagnosis, and access to specialized care. Many individuals manage their symptoms into adulthood, although some may experience progressive challenges over time. Outcomes described in medical literature continue to evolve as standards of care improve, underscoring the importance of ongoing monitoring and support. Connecting with a genetic counselor and specialized care centers can provide valuable guidance for families navigating this condition.