Muscular Dystrophy Breaks Down The Muscle Fibers example essay topic

Muscular dystrophy refers to, not one, but a group of muscle diseases. These diseases have three features in common: they are hereditary; they are progressive; and each causes a characteristic and selective pattern of weakness. Duchenne muscular dystrophy (DMD) is the most prevalent and severe childhood form of this group of diseases. Each form of muscular dystrophy is caused by a defect in a specific gene. In 1986, scientists discovered exactly which piece of genetic material is missing in Duchenne muscular dystrophy patients. They named it for Guillaume Benjamin Am and Duchenne (1806-1875), a French neurologist who was one of the first doctors to discover and study the disease.

When functioning properly, the Duchenne gene carries instructions for assembling a muscle protein known as dystrophic. At about 2,500,000 nucleotides, dystrophic is one of the largest genes known. Dystrophin is largely responsible for reinforcing and stabilizing the sarco lemma. Dystrophin associates with the muscle fiber sarco lemma by interacting with the actin micro filaments and with a trans membrane protein complex linked to the extracellular matrix. This latter dystrophic-associated glycoprotein complex (DAGC) includes the extracellular, [Alpha]-, which binds to me rosin in muscle fiber basal laminae, as well as a number of other integral and cytoplasmic membrane proteins: [Alpha]-; [Alpha]-, [Beta]- and [Gamma]- (see Figure 1). The DAGC provides a physical link and, potentially, a signaling pathway between the extracellular matrix and the internal scaffolding of the muscle cells.

Mutations in the Duchenne gene result in dystrophic deficiency, which constitutes the pathogenic basis of DMD. Dystrophin is either absent or severely deficient in a person with DMD. When dystrophic is lost through gene mutation, the muscle falls apart under the tension generated when it contracts. Without dystrophic, the muscle fibers also lose their ability to regenerate and are eventually replaced with adipose tissue and fibrous connective tissue (see Fig. 2 and Fig. 3). The Duchenne gene has been located on the short arm of the X chromosome. This means that Duchenne muscular dystrophy is inherited as an X-linked recessive disease.

Females have two X chromosomes, while males have one X chromosome and one Y chromosome. Therefore, in females, a normal X chromosome can mask a disease carrying X chromosome. In males, who only have one X chromosome, an X chromosome disease has to be expressed. This is why DMD usually only affects males, with rare exceptions. Men with DMD will pass on the defective gene to their daughters, making them carriers, but never to their sons. A carrier has a 50% chance of passing the gene for DMD to her daughter, who will also become a carrier.

The son of a carrier also has a 50% chance of being affected (see Fig. 4). Mothers of boys who have DMD are not necessarily carriers. The child could have been affected by a new mutation. Duchenne muscular dystrophy, being an inherited disease, is present from the very first stages of fetal development. Yet, at the time of birth there is no physical indication that there is anything abnormal.

It isn't until between the ages of 18 months and 4 years that developmental problems start to become apparent. Usually, the first signs parents notice is that the affected boy starts walking at a later age than average. DMD boys tend to fall down more often, have difficulty getting up from the floor and climbing up stairs. They also develop a tendency to walk on their toes.

Affected boys are unable to keep up with normal children their age and are considered clumsy. By the age 3 to 5 years, generalized muscle weakness becomes more obvious. Weakness and wasting usually begins in the ilio psoas, quadriceps and gluteus muscles and soon spreads to involve the anterior tibial group. In upper limbs, the costal origin of pectoralis major, the latissimus dorsi, the biceps, triceps and brachio radialis muscle are the first involved. Calf muscles, and sometimes other muscles, are noticeably larger while other muscles are poorly developed.

Parents may be falsely encouraged by a seeming improvement between the ages of 3 and 7, but this may only be due to natural growth and development. As the affected boy ages, the rate of regeneration can no longer keep up with the rate of degeneration and the number of healthy muscle fibers declines as does the strength of the muscle. Muscle wasting, a waddling gait and an accentuated spinal curvature, termed lordosis, become evident as the disease progresses. After age 8 or 9, weakness progresses rapidly, resulting in the inability to walk or stand alone.

Leg braces may make walking possible for a year or two, but by early adolescence walking becomes impossible. By their teenage years, a wheelchair is needed constantly. In the late stages of Duchenne muscular dystrophy there is a noticeable shortening of muscles and loss of muscle tissue. This results in the inability to move the major joints of the body. By the time DMD boys are in their 20's, their muscles have degenerated to the point that they no longer function. At this time they usually die due to respiratory failure.

Boys with Duchenne muscular dystrophy have to not only deal with their muscles wasting away but with other health and / or intellectual problems. Sometimes, diagnosis is brought about by the parents concern of an intellectual handicap. While only a minority of boys with DMD are mentally retarded, it is more frequent than in other children. Unlike the muscle weakness, any intellectual handicap an affected boy may have, is not progressive. Whatever intelligence the child is born with, whether he is of superior, average or less than average intelligence, is what he retains unless affected by something else.

As mentioned in a previous paragraph, movement of the joints becomes difficult, if not impossible. A contracture is when a joint's range of motion begins to become restricted. Contractures can be seen early on in the ankles, then in the hips and knees and lastly in the upper limbs. Physiotherapy and occupational therapy are aimed at keeping contractures at bay as long as possible. Sometimes surgery can be used to correct a contracture.

Surgery can also be used upon the complication of scoliosis. If the scoliosis is severe it can interfere with the function of the lungs and upper limbs. More and more often, scoliosis is being treated with surgery by inserting a metal rod into the spine to hold it straight. Care has to be taken as to when surgery can be done as the safety of surgery decreases as the age of the DMD boy increases.

Another major health problem of those with DMD is the weakening of the respiratory muscles. The function of the lungs in people with DMD depends mostly on the strength of the muscles that move the chest in breathing and coughing. The strength of these muscles is the main factor determining the length of an affected person's life. When these muscles weaken, the capacity of the lungs diminishes.

Then the lungs stop functioning adequately, resulting in not enough oxygen and too much carbon dioxide in the blood. The imbalance between oxygen and carbon dioxide causes headaches, drowsiness and a general lack of well being. Assistance with breathing though a face mask may alleviate those symptoms by bringing the oxygen and carbon dioxide levels back into balance. The muscles involved in respiration continue to weaken until breathing can no longer be sustained without the use of a machine. Currently, prenatal genetic counseling is the best way to determine the chances of a woman giving birth to a child with DMD. Such counseling is strongly recommended for women who have had males in their family affected by the disease.

To find out if a boy has DMD, there are four types of testing. One type is a DNA blood test. This is where the X chromosome is analyzed to see if the Duchenne gene is either absent or mutated. The creatine kinase (CK) test checks the amount of creatine kinase in the blood.

CK is an enzyme that is very important for the production of energy within the muscle fibers. The muscular dystrophy breaks down the muscle fibers causing the CK to leak out into the blood. Those who have DMD have a significant amount of creatine kinase in their blood. An EMG (electromyography) can measure the pattern of electricity within a muscle. By inserting a needle through the skin and into a muscle, the pattern of electricity of a contracting muscle can be recorded.

If the pattern is abnormal, that means the muscle is also abnormal. The last type of test is a muscle biopsy. A small piece of muscle is removed, cut into thin slices and dyed with a variety of dies to then be viewed under a microscope by a pathologist. Muscle cells of a person with DMD are very distinctive from normal muscle cells (see Fig. 5). Of these tests, two can be performed in utero (the CK test from a fetal blood sample and a muscle biopsy) but both have a limited reliability. There are currently different types of treatment for Duchenne muscular dystrophy.

They do not stop the disease but they often slow it's progression. Care is aimed at managing the symptoms of the disease to optimize the quality of life. Activity is one of the best ways to stave off the eventual effects of DMD. Inactivity, such as bed rest, will only contribute to muscle wasting.

Individualized physical therapy regimens started at the time of diagnosis promote flexibility, delay the onset of contractures and may be helpful to maintain muscle strength and function. Occupational therapy and aids such as leg and ankle braces can also help. A nutritional diet and vitamins are another way to help maintain the affected person's quality of life. Some boys with DMD seem to have highly benefited from a good diet and vitamins while others show no noticeable improvement. The same can be said about the treatment with drugs such as. Studies have shown that can cause initial improvement in muscle strength and may slow the progress of DMD as much as 3 years.

Side effects have to be taken into account, though. They include weight gain, potassium loss, behavioral change, acne, insomnia, high blood pressure, weak bones and many others. There are other drugs available (, , , etc.) but is the most widely used. The above treatment and care methods, when used in combination, can improve the DMD sufferer's quality of life and often help prolong it. To date, there is no cure for Duchenne muscular dystrophy. There are many organizations and scientists who are constantly working to find a cure.

At this time, one avenue of research is gene therapy. Scientists have been trying to inject a dystrophic gene into affected muscles in hopes that it will replace or repair the DMD gene. So far, this method looks very promising in trials with mice and dogs. They have been able to get the gene past the body's immune system. Still, the researchers have to figure out how get only one gene in the right cell, how to keep the gene from impairing any other functions and how to get the gene to produce the right amount of protein. Some researchers are trying a different approach; that of my oblast transfer therapy.

This school of thought attempts to fuse healthy, immature muscle cells with dystrophic cells to make hybrid muscles that function normally. Unfortunately, initial tests have not fared very well because the injected my oblasts do not seem to travel very far from the injection site. The last type of research deals with a protein called. It is hoped that this protein could functionally take over for dystrophic. Scientists are trying to discover a chemical that will up regulate production without disrupting anything else in the body.

Until a cure is found 1 in approximately every 3,500 boys will inherit Duchenne muscular dystrophy and eventually die from it. The current treatments only place a temporary obstacle in front of the disease. It is hoped that advancements in the fields of science and medicine will help to speed along the discovery of a cure for this debilitating muscular disease.