GNE myopathy
GNE myopathy is a progressive genetic muscle disorder that causes skeletal muscle weakness, typically starting with foot drop in late adolescence or early adulthood while sparing the quadriceps.
Overview
GNE myopathy is a condition that primarily affects skeletal muscles, which are the muscles the body uses for movement. This disorder causes muscle weakness that typically appears in late adolescence or early adulthood and worsens over time.
Symptoms
The symptoms of GNE myopathy progress gradually and are characterized by:
- Difficulty lifting the front part of the foot (foot drop), which is often the first sign of the condition. This is caused by weakness in the tibialis anterior muscle of the lower leg.
- Altered gait, making it difficult to run and climb stairs.
- Progressive weakness in the muscles of the upper legs, hips, shoulders, and hands.
- Sparing of the quadriceps (the large muscles at the front of the thigh), which are usually unaffected.
- No involvement of the eye or heart muscles, and no associated neurological problems.
- Increasing difficulty walking, with most affected individuals requiring wheelchair assistance within 20 years of symptom onset.
Frequency
Worldwide, fewer than 9 in 1,000,000 people are estimated to have GNE myopathy, though the actual number may be higher due to undiagnosed cases. The condition is more frequent among Japanese, Iranian Jewish, and Indian subcontinent populations.
Causes & Genetics
GNE myopathy is caused by variants (mutations) in the GNE gene. This gene provides instructions for making an enzyme involved in the chemical pathway that produces sialic acid, a simple sugar that attaches to the ends of complex molecules on cell surfaces.
Sialic acid influences several cellular functions, including:
- Cell movement (migration).
- Cell-to-cell attachment (adhesion).
- Signaling between cells.
- Inflammation.
Variants in the GNE gene reduce the activity of the enzyme, decreasing sialic acid production. This shortage leaves less sialic acid available to modify cell surface molecules. Researchers are still investigating why this shortage of sialic acid specifically leads to progressive muscle weakness in skeletal muscles while other tissues remain unaffected.
Associated Gene
- GNE
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. Parents of an affected individual each carry one copy of the altered gene but typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Distal myopathy with or without rimmed vacuoles
- Distal myopathy with rimmed vacuoles (DMRV)
- Distal myopathy, Nonaka type
- Hereditary inclusion body myopathy type 2 (HIBM2)
- IBM2
- Inclusion body myopathy type 2
- Inclusion body myopathy, hereditary, autosomal recessive
- Inclusion body myopathy, quadriceps-sparing
- Nonaka distal myopathy
- Nonaka myopathy
- QSM
- Quadriceps-sparing myopathy