GNE myopathy

GNE myopathy is a muscle disorder that primarily affects the distal muscles, most causing weakness in the lower limbs. It is caused by pathogenic variants in the GNE gene and is inherited in an autosomal recessive pattern. The condition is uncommon, affecting approximately 1 to 9 individuals per 100,000 people. Most affected individuals experience symptoms in early to mid-adulthood, although the age of onset may vary.

Patients with GNE myopathy typically present with progressive weakness in the distal lower limb muscles, which has been documented in a significant proportion of affected individuals. This muscle weakness is usually the leading symptom that prompts further medical evaluation. As the condition evolves, some individuals may experience difficulties with mobility and daily activities, although the rate of progression and severity of symptoms can vary widely. Not all individuals experience all features, and severity varies considerably.

GNE myopathy is caused by pathogenic variants in the GNE gene, which plays a critical role in the biosynthesis of sialic acid, an important component for muscle cell function. The disruption of this gene’s function leads to muscle weakness and degeneration over time. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the altered gene, one from each parent, to be affected. Families may benefit from genetic counseling to understand recurrence risks and implications for family planning.

Currently, management of GNE myopathy focuses on supportive care and symptom management, as there are no FDA-approved treatments specific to this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include physical therapy and occupational therapy to maintain muscle function and mobility. In addition, some orphan drug designations are under investigation, highlighting ongoing research into targeted therapies, though these are not yet available as standard treatment options. Genetic counseling is recommended to help patients and families navigate treatment choices and future planning, and patients should discuss management options with their healthcare team.

The course of GNE myopathy is variable, with some individuals experiencing a steady progression of muscle weakness while others may see periods of relative stabilization. With current standards of care, many individuals continue to manage their symptoms into adulthood and quality of life has improved over recent decades. Outcomes described in medical literature continue to evolve as standards of care improve, and the long-term trajectory can differ widely among patients. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition to better understand potential future needs and care strategies.

Several clinical trials are currently investigating new treatment approaches for GNE myopathy. Individuals interested in learning more about emerging therapies can search ClinicalTrials.gov or consult their care team about eligibility for these studies.