What is GNE Myopathy?


GNE myopathy is a rare, autosomal recessive disorder which causes progressive skeletal muscle weakness and atrophy.

GNE myopathy was also known as:

  • hereditary inclusion body myopathy (HIBM)
  • inclusion body myopathy type 2 (IBM2)
  • Nonaka myopathy

GNE myopathy has a high prevalence in the Jewish population where almost 1 in 500 people present with the condition. The general prevalence is thought to be 1 in a million people. The National Human Genome Research Institute estimates at least 40,000 cases worldwide with almost 13,000 in Asia. GNE myopathy can go undiagnosed for several years and this may be the reason for the muted numbers of those affected.

Currently there is no approved therapy for GNE myopathy. Mouse models for gene therapy are in progress. The National Institute of Health is also researching the possibility of using N-acetyl-D-mannosamine (ManNAc). ManNAc is an intermediate molecule involved in the production of sialic acid within cells. Patients with GNE myopathy usually have insufficient sialic acid produced in the muscle cells which leads to muscle wasting. Mouse models using ManNAc have showed increased production of sialic acid thereby improving muscle function.

Patterns of Inheritance


Patterns of Inheritance
GNE myopathy is an autosomal recessive condition
Image Source: Pixabay

GNE myopathy is an autosomal recessive disorder which means both parents have the carrier gene with 25% chance of each child having the disease. GNE Myopathy is caused by various mutations in the GNE gene (which produces an enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase). A child with GNE Myopathy inherits two copies of the mutated GNE gene from each parent and hence expresses the disease.

The enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase is critical for the production of sialic acid in the cell. Incorrect coding of the enzyme results in insufficient levels of sialic acid leading to the degeneration of muscle cells. .

Signs and Symptoms


Some of the early signs of GNE myopathy include:

  • Stiffness
  • Tightness
  • Pain
  • Tenderness
  • Change in gait
  • Falling
  • Difficulty in walking fast, running and climbing stairs

Muscle weakness and fatigue is a common symptom of GNE myopathy and individuals may experience strain with light physical activity.

Diagnosis


GNE myopathy is often hard to diagnose because of generalized symptoms. A good orthopedist or neurologist take a detailed medical history and look for key signs like foot drop and frequent falls. Some of the tests that are used to diagnose GNE myopathy include:

  • biochemical tests - tests like Creatine Kinase (CK) which is a marker of muscle degeneration
  • molecular test - DNA tests like Next Generation Sequencing (NGS) to confirm the presence of the mutated GNE gene
Please see list of specialized genetic testing centres
diagnosis
GNE Myopathy can be diagnosed with biochemical or molecular tests
Image Source: Pixabay

Treatment and Management


Currently, no permanent cure is available for GNE myopathy. Treatment is aimed at preventing complications and enabling independent living. An interdisciplinary team of doctors including neurologists, orthopedicians and physiotherapists will be required to take care of the clinical needs of the individual. In the early stages when just diagnosed, it is important to start physiotherapy and exercises to prevent further degeneration of muscles. Diet management is important to avoid gaining weight and over burdening the muscles.

Investigational therapies like gene therapy and gene editing are in the clinical research stage and proving to be exciting.

Living with GNE Myopathy


Individuals with GNE myopathy must be encouraged to participate in all life activities. Genetic counselling and psychosocial counselling must be made available whenever required with other supportive measures.

Look up our list of patient organizations in India for help and support
Living with GNE myopathy
Individuals must be encouraged to engage in physical activities
Image source: Pixabay

Prenatal Testing and GNE myopathy


If there is a known case of GNE myopathy in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.

If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.

Look up our list of clinical geneticists and testing centres in India for help and support

Mail us on namitha@strandlf.org if you require any further information or want to contribute a resource for this page

Article and Journal Links:


Videos:


What is GNE myopathy?

Shubraa Sinha: GNE Myopathy - Moving the 'awareness' needle: Blue Ribbon Symposium 2018