Research & Explain the Duchenne Muscular Dystrophy Disease (Essay Sample)

Duchenne Muscular Dystrophy
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Abstract
Duchenne muscular dystrophy (DMD) is an X-linked disorder. The disease affects muscles leading to progressive degeneration and muscle weakness. The genes that cause the disease are recessive and code for the protein dystrophin. The protein is one of the several cell membrane proteins in the muscle cell that form the dystrophin-glycoprotein complex. The complex is vital role in the maintenance of the muscle cell integrity. Therefore, lack of any of the proteins of the complex will lead to pathology, resulting in muscle wasting. The absence of dystrophin leads to DMD.
Introduction
Duchenne muscular dystrophy is an inherited condition that leads to muscle weakness and progressive degeneration. It is caused by the absence of the necessary dystrophin protein responsible for muscle integrity. The absence is caused by a mutation in the DMD gene. The gene responsible for DMD is a complex gene (Behrman, Kliegman & Jenson, 2011). It measures about 2,400 kb and has 79 exons. It is located at XP21.1 of the X-chromosome in the human genome. It is one of the biggest genes in humans. The gene encodes for a 420 kDa protein, dystrophin (Nowak & Davies, 2004). The protein has many isoforms depending on the location. These include the tissue-specific protein, CNS proteins, the proteins in Schwan cells of peripheral nerves and other tissues such as cardiac muscle, skeletal muscle, embryonic and smooth muscles. In the muscles and neurons, the protein is found in the cell membrane and myo- tendinous junctions (Emery, 2003).
Etiology
Duchenne muscular dystrophy is a common X-chromosome linked muscle disorder. It was first noted by Guillaume Benjamin Duchenne, a French neurologist, in the 1860s. Little was known about the disease till the 1980s when the mutated gene on the X-chromosome was identified. The protein, dystrophin, which was associated with the gene, was identified in 1987 (mda.org). Lack of the protein in the cells of the muscle makes them fragile and easily damaged.
Duchenne muscular dystrophy is caused by a mutation in a recessive gene on the X-chromosome and occurs in about 1:3500 males (Nowak & Davies, 2004). Males are more fully affected by the DMD disease as they have one X chromosome. They inherit the mutated gene from the mother. Females are mostly carriers though they can experience a less severe form of the DMD. The gene that is mutated to cause Duchenne musclar dystrophy (DMD) codes for the protein dystrophin. About 40% of DMD gene mutations are small frame-shift rearrangements or point mutations while about 60% are large deletions or insertions leading to frameshift errors downstream. Dystrophin protein normally helps maintain the integrity of the muscle cells. The protein hence is found missing in DMD. When the function of the protein is reduced, or it is partially expressed, the condition is referred to as Becker disease, a mild variance of DMD (Behrman, Kliegman & Jenson, 2011).
Pathophysiology
Dystrophin protein plays a primary role in the muscle as the linkage of the internal cytoskeleton to the ECF. The amino terminus of the protein binds to the carboxyl terminus of the dystrophin-associated protein complex and F-actin at the sarcolemma. The complex (also known as DAPG) is also composed of sarcoglycans, dystroglycan, integrins, and caveolin. A mutation in any of these components causes muscle dystrophy. In the absence of dystrophin protein, the DAPC becomes destabilized. This leads to diminishing of the levels of the member proteins, leading to progressive fiber damage and leakage of the membrane. The loss of DAPG, which also has a signaling role, leads to the pathogenesis (Deconinck & Dan 2007).
Signs and Symptoms
The disease is hereditary, and hence the symptoms can appear as early as infancy but delayed symptoms appear before the age of six years. The symptoms of DMD are usually muscle related. They include muscle weakness, difficulty with motor skills, fatigue, and breathing difficulties. The patients often experience trouble waking up or even walking. The children may also present with low IQ and learning difficulties. The symptoms progress with age and become severe. There may be a permanent loss of the ability to walk by the age of nine years. By the age of twelve, the DMD patients are bound to wheelchairs. Most of them die in the late teenage or early twenties of respiratory failure. According to Behrman, Kliegman and Jenson (2011), the male patients show an abnormal cardiogram by the age of eighteen, hence showing problems with the cardiac muscle and diaphragm.
A complete neurological, cardiac, muscular and lung exam may show different signs. The patient may present with cardiomyopathy, congestive heart failure resulting to arrhythmias, scoliosis (deformities of chest and back), muscle mass wasting and muscle deformities. Other muscle signs that the patient might present include contractures and pseudohypertrophy (replacement of muscle with fats). In the late stages, the patient presents with respiratory disorders such as pneumonia (Emery, 2003).
Diagnosis
There are various tests that can be utilized to make a diagnosis of DMD. These include muscle biopsies, electromyography (EMG), genetic testing and serum creatine phosphokinase (CPK). The genetic screening is the definitive diagnosis for the disease. EMG result can be used hand in hand with the results of the other tests to give a clue to the muscle dystrophies but won’t confidently point to DMD (Behrman, Kliegman & Jenson, 2011). The signs and symptoms should always be supported by the laboratory diagnosis for a better treatment of DMD. Constant monitoring of the patients should be employed to ensure the therapy is working (Emery, 2003).
Treatment
There has been no definitively developed treatment for DMD. All therapies and treatments give to DMD patients are intended to alleviate the symptoms and signs. They include drugs designed to slow down the degeneration of muscles and improve the quality of life of the patient. There has been no explained effectiveness of the supportive therapies currently administered. Steroids are administered to slow down the muscle wast...