GNE myopathy

GNE Myopathy GNE Myopathy, also known as Hereditary Inclusion Body Myopathy (HIBM), Nonaka Myopathy, or Distal Myopathy with Rimmed Vacuoles, is a rare genetic disorder characterized by progressive muscle weakness and atrophy. This condition primarily affects the skeletal muscles, particularly those in the lower limbs.

Etiology

GNE Myopathy is caused by mutations in the GNE gene, which encodes the enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. This enzyme is crucial in the biosynthesis of sialic acid, a sugar molecule important for muscle function.

Pathophysiology

The deficiency in sialic acid production due to GNE mutations leads to the accumulation of abnormal proteins in muscle cells, forming rimmed vacuoles and causing muscle fiber degeneration. The exact mechanism by which sialic acid deficiency leads to muscle pathology is still under investigation.

Clinical Features

GNE Myopathy typically presents in early adulthood, with symptoms such as:

• Progressive muscle weakness, especially in the distal muscles of the legs.
• Difficulty in walking and frequent falls.
• Weakness in the hands and arms as the disease progresses.

Diagnosis

Diagnosis of GNE Myopathy involves:

• Clinical evaluation of symptoms and family history.
• Muscle biopsy showing rimmed vacuoles and other characteristic histopathological features.
• Genetic testing to identify mutations in the GNE gene.

Management

Currently, there is no cure for GNE Myopathy. Management focuses on:

• Physical therapy to maintain muscle strength and mobility.
• Orthotic devices to assist with walking.
• Research into potential therapies, including sialic acid supplementation and gene therapy, is ongoing.

Prognosis

The progression of GNE Myopathy is variable, but it generally leads to significant disability over time. The rate of progression can differ among individuals, and some may require mobility aids or become wheelchair-dependent.

Research

Ongoing research is focused on understanding the pathophysiology of GNE Myopathy and developing effective treatments. Clinical trials are exploring the efficacy of sialic acid supplementation and other therapeutic approaches.

See Also

• Muscular Dystrophy
• Genetic Disorders
• Rare Diseases
• Nonaka, I., et al. "Distal myopathy with rimmed vacuoles: a clinicopathologic study of 24 patients." Annals of Neurology 15.3 (1984): 267-272.
• Huizing, M., et al. "GNE myopathy: new insights and new therapeutic options for an ultra-rare disorder." Neurotherapeutics 11.4 (2014): 763-771.

NIH genetic and rare disease info

• NIH info on GNE myopathy

GNE myopathy is a rare disease.