ASPIRE Educational Series: GNE Myopathy- Part 4

GNE Myopathy is a rare, severe and progressive muscle disease that affects both the upper and lower limbs in adults. GNE Myopathy is caused due to a deficiency in enzyme (GNE/MNK) which hinders the biosynthesis of sialic acid, which is vital for the modification of muscle proteins and fats. When sialic acid levels are low, the muscles begin to weaken, resulting in loss of strength and muscle function.

GNE is an abbreviation for the mutated gene (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). The condition is described by several other names:

GNE Myopathy is an autosomal recessive disease. Hence both parents (usually unaffected carriers) can pass on a defect copy of the GNE gene to their affected child. There is a 1 in 4 chance that an individual will develop GNE Myopathy if both parents are carriers.

The disease generally has an adult onset which usually starts around the age of 20-30 years, although onset of symptoms have been seen in individuals as young as 17 and as old as 52. It therefore affects the most productive time of a person’s life. Early symptoms typically include ‘foot drop’ (difficulty lifting the front part of the foot), which causes tripping and lack of balance. As the disease progresses, difficulties climbing stairs, getting up from a sitting position and weakness in hand and shoulder muscles is usually noticed. It can lead to severe disability within 10 – 15 years, confining many to a wheelchair. It does not seem to affect the brain, internal organs or nerve sensation. The quadriceps are relatively spared, and remain strong until the late stages of disease.

GNE myopathy is a disorder found worldwide, however, until recently it was mostly recognized in patients of Japanese and Persian Jewish ethnicity, where founder mutations are prevalent. The worldwide prevalence of GNE myopathy is estimated at 1/1,000,000 with higher prevalence seen in Middle Eastern Jews and Japanese population.

Owing to its ultra-rare status, diagnosis of GNE Myopathy is a challenge. It is often misdiagnosed for other conditions with similar symptoms, such as Limb-Girdle Muscular Dystrophy, Charcot-Marie-Tooth disease or Miyoshi myopathy. Diagnosis may require the efforts of a multidisciplinary team such as primary care physicians, neurologists, and neuromuscular specialists. a neurologist generally performs a detailed physical exam as well as tests to determine the cause of muscle weakness. If a myopathy is suspected, possible tests include:

Currently, there are no approved treatments for GNE Myopathy. It is managed by symptom treatment and evaluated and managed by a multidisciplinary team including neurologists, geneticists and physiatrists, as well as physical and occupational therapists.

Current treatment theories revolve around the following basic concepts:





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