User:EKallsen/sandbox

Mechanism

        Diseases in the nemaline myopathy group come about from the presence of rod-like structures running parallel to the sarcomeres in skeletal muscle fibers. The presence of these rods in muscle cells makes it more difficult for the muscles to contract.   Normally, muscle cells contract by different fibers slide past one another.  The structures in the muscle cells created by these fibers are called sarcomeres.  All of the different gene mutations leading to NM that have been found so far are in genes that encode different aspects of the sarcomeres. In normal muscle cells, the different kinds of fibers in the sarcomeres are distributed evenly.  Evidence suggests that some kind of NM affect the arrangement of these fibers, causing the muscles to be unable to contract as efficiently.
        Nemaline Myopathy is usually genetic and shows traits in the affected individual from birth or an early age.  However, there are some cases of symptoms of NM not showing up until adulthood.  These cases are usually not genetic. Of the genes that have been linked to nemaline myopathy, most are also involved in encoding proteins in the sarcomeres in the muscle cells.  Respiratory muscles are often more affected than other skeletal muscle groups.  Cardiac muscles usually function normally in those affected by Nemaline Myopathy.  
       The different genes whose mutations lead to the different kinds of nemaline myopathies affect the cells and the person’s body differently.  The first kind of nemaline myopathy identified is due to the Slow α-Tropomyosin Gene TPM3 and varies from case to case with its severity.  In this kind of nemaline myopathy, affected people are weaker and see greater weakness in their lower limbs than their upper limbs. 
        A kind of nemaline myopathy caused by a mutation in the Nebulin Gene, NEB, also has a large range of severity.  All identified cases where nemaline myopathy is caused by a mutation in this gene have been recessive.  Patients with this kind of NM are more affected in the muscles in their head, rather than their proximal muscles at the core of their body.  Consequently, patients with this genetic mutation often cannot lift their heads.  There have been cases with evidence that people this kind of NM may have higher intellect.  
        A third kind of nemaline myopathy in the Skeletal Muscle α-Actin Gene ACTA1 is due to a recessive null mutation.  These patients do not always show the typical nemaline bodies in their muscle cells.  The only abnormality they show is an abnormal distribution of muscle fibers. 
        There are several other identified kinds of mutations that lead to Nemaline Myopathies.  One affects slow skeletal muscles, one leads to the formation of both nemaline bodies and other abnormal, core-like, structures forming in the patient’s muscles.  

        Although patients early on often have mobility in their joints that is past the normal range, as they age, joint deformities and scoliosis usually occur.   If the person with Nemaline Myopathy keeps an eye on his or her joints early on, the problems with them can be detected when they begin and their progression can be delayed.  Treatment of joint problems ranges from stretching exercises with physical therapy to surgical introduction of braces.  The benefits of exercise in people with nemaline myopathy are still being studied, however, researchers have seen improvements in muscle function from low-intensity exercise. Vigorous exercise and the use of heavy weights should be avoided.

Treatment

        Nemaline Myopathy is a very rare disease that only affects 1 out of 50,000 on average, although recent studies show that this number is even smaller. At present, Nemaline Myopathy does not have a cure. There are a number of treatments to minimize the symptoms of the disease.  The treatments and procedures to help patients with nemaline myopathy vary depending on the severity of the disease. 

As people with NM grow and develop throughout their lives, it is important for them to see a variety of doctors regularly, including a neurologist, physical therapist, and others, such as speech therapists and psychologists, to help both the patient and family adjust to everyday life.

Current Research

        Research today on NM seeks to better understand the molecular effects the gene mutations have on both muscle cells and the rest of the body. Research is also being done to observe any connections NM has to other diseases and health complications.