What is GNE Myopathy?
GNE Myopathy (GNEM) is a form of muscular dystrophy. Muscular dystrophies are conditions that are characterized by progressive muscle weakness and muscle wasting. Individuals with GNEM begin having symptoms in their late teens or young adulthood.
The condition is progressive, which means the muscles get weaker over time. The muscles affected in GNEM are the skeletal muscles. Skeletal muscles are the ones attached to bones that the body uses to move. Muscle weakness generally starts in the lower leg muscle called the tibialis anterior. When this muscle becomes weak, it changes the way a person walks. Also, foot drop, where lifting of the front part of the foot becomes difficult, is an early symptom. Eventually, the ability to run and climb stairs becomes difficult. Other muscles become weak as the condition worsens, including those of the upper legs, hips, shoulders and hands. However, the quadriceps muscles (found in the front part of the thighs) usually do not show any signs of weakness. Due to progressive weakness in the leg muscles and difficulty walking, individuals usually need a wheelchair about 10 to 20 years after the first signs and symptoms appear. The muscles of the eyes and face, those used for breathing and digestion as well as the heart muscles are not usually affected.
GNEM is caused by a change/mutation in the gene called GNE. This gene contains instructions for an enzyme that helps make a sugar called sialic acid. Sialic acid has many jobs to help the muscles work correctly. Some of those jobs include helping the cells stick together (adhesion), movement of the cells (migration) and communicating between the cells (signalling). Lack of sialic acid causes the muscles to weaken over time.
GNEM is inherited in an autosomal recessive manner. We each have two copies of the GNE gene. One copy came from our mother and the other copy came from our father. We only need one copy to be working correctly in each cell. However, people with GNEM have two copies of the GNE gene that are not working correctly. Since people who have no working copies of GNE are the only ones who have symptoms if GNEM, we say this is inherited in an autosomal recessive pattern. Someone who only has 1 change is known as a "carrier". Carriers do not show signs of GNEM. Unaffected parents of people with GNEM are "obligate carriers." This means that they are each a carrier of a gene change in GNE, but have another copy of the GNE gene that is working correctly. When two carriers have children, there is a 25% chance with each pregnancy that they will have a child with GNEM. There is a 50% chance with each pregnancy that the child will be a carrier like his or her parents. Finally, there is a 25% chance with each pregnancy that the child will neither be a carrier nor have GNEM.
OMIM 07 Mar. 2016 http://www.omim.org/entry/605820
National Center for Advancing Translational Science. Genetic and Rare Disease Information Center. 07 Mar. 2016. https://rarediseases.info.nih.gov/gard/9493/inclusion-body-myopathy-2/resources/1
Neuromuscular Disease Foundation. 14 Mar. 2016. http://www.ndf-hibm.org/index.php/about-hibm