Duchenne muscular dystrophy (DMD) is an inherited genetic condition that affects about two out of every 10,000 people. Due to the inheritance pattern of DMD, males are more frequently affected with the disease than females (about 1 in 3,500 males is affected with DMD). DMD is part of a group of hereditary muscle diseases called muscular dystrophies.
Patients with DMD experience a progressive degeneration of muscle function beginning in infancy or early childhood. The loss of muscle function usually starts in the pelvis and the legs and eventually spreads to all parts of the body. Patients with DMD first lose the ability to walk, and eventually they lose the ability to move other parts of their bodies, such as the arms.
DMD is caused by a defect, or mutation, in a gene that contains instructions for making dystrophin, a protein that normally helps to maintain the structure and function of muscle. Individuals with DMD have reduced levels of this protein, so the muscles cannot carry out normal functions. Becker muscular dystrophy is another type of muscular dystrophy that is caused by a different type of mutation in the dystrophin gene.
Many patients with DMD eventually experience heart and/or lung complications, due to deterioration of muscles in these organs. This may lead to an inability to pump blood or breathe normally.
Most individuals with DMD do not survive past 30 due to the complications of muscle deterioration.
There is currently no known cure for DMD. However, some treatments exist that may help manage the symptoms, such as the use of walking devices to assist with moving and ventilators to assist with breathing.
DMD is a recessive inherited genetic condition. Normal individuals have two copies of most genes (one inherited from the father and one from the mother). In a recessive genetic disorder, both copies of a certain gene need to be defective for the condition to manifest itself. It has been shown that mutations in the dystrophin gene, which is located on the X chromosome, may cause DMD.
Females have two copies of the X chromosome, but males have one X chromosome and one Y chromosome. Males inherit an X chromosome from the mother and a Y chromosome from the father, so a male can only inherit the dystrophin gene from the mother. Therefore, a female needs to inherit two mutant copies of dystrophin to develop DMD (one from each parent), whereas a male only needs to inherit one mutant copy of dystrophin to develop the condition.
Because females need to inherit two mutant copies of dystrophin to develop the condition, whereas males only need to inherit one mutant copy, DMD is more common in males than females. An estimated one out of 10,000 people is affected with DMD, whereas one out of 3,500 males is affected with the disease. Females who inherit only one mutant copy of dystrophin are called "carriers." Females who are carriers may exhibit some mild symptoms.
DMD is caused by a defect, or mutation, in the DMD gene, which provides the instructions for making a protein called dystrophin. The mutation prevents the full-length protein from being produced. This protein normally helps maintain the structure and function of muscle cells. Individuals with DMD have an absence of this protein, so it can't carry out its normal function. Although the reasons are not clearly understood, muscle cells lacking dystrophin eventually die.
About two-thirds of cases of DMD are inherited, meaning that a defective DMD gene was transmitted from a parent to the child. However, about one third of cases of DMD are not inherited, but instead result from a random mutation in the egg or sperm or in early embryonic development.
DMD is a recessive X-linked condition, meaning that the dystrophin gene is located on the X chromosome and that all copies of the dystrophin gene need to be defective for an individual to develop the condition. Because females have two X chromosomes, they need to have two mutant copies of dystrophin to develop DMD. If a female has one mutant copy and one normal copy, the normal copy will make enough dystrophin to compensate for the mutant copy and any symptoms will be very mild. Because a male has one X chromosome and one Y chromosome, males only need to have one mutant copy of the dystrophin gene to develop the condition. This is because males don't have a second dystrophin gene that can serve as a backup.
SIGNS AND SYMPTOMS
Muscle deterioration: Patients with DMD experience a progressive degeneration of muscle function starting in infancy or in early childhood (around age six). The loss of muscle function usually starts in the pelvis and the legs, but eventually spreads to all parts of the body. An infant or child may stumble, waddle, or have difficulty climbing stairs due to impaired leg function. The ability to sit or stand is often affected too. It may be difficult to diagnose DMD just based on these symptoms, so if DMD is suspected, additional tests may be needed.
In patients with DMD, the muscles may become enlarged and eventually the muscle tissue is replaced with fat and connective tissue, a process called pseudohypertrophy. Muscle enlargement is especially noticeable in the calf muscles. This causes the muscle to progressively waste away and by age 12 most patients lose the ability to walk. Many patients experience loss of strength and endurance. As a patient gets older, other muscles throughout the body become affected, such as the arms, back, neck, and shoulders. Eventually, patients may completely lose the ability to move and become paralyzed.
Contractures: Many patients experience joint contractures, which is a stiffening of muscles around joints that can make it difficult and painful to move or lock the joints in positions.
Mental defects: For unknown reasons, about one-third of patients with DMD have learning disabilities or exhibit mental defects.
Carrier females: Females who are "carriers" (they have one normal copy of the dystrophin gene and one mutant copy) for DMD may exhibit some mild symptoms, including some muscle weakness or cramping. However, complete loss of muscle function typically doesn't occur in carrier females, and symptoms are generally milder than in males. Carrier females may exhibit symptoms early in life, and in some cases, symptoms may grow progressively worse.
Physical signs: The first step in diagnosing DMD typically begins with a clinical exam in which a doctor looks for physical signs of the condition, especially weakened muscles or loss of muscle function. If DMD is suspected, other tests may be used to confirm a diagnosis.
Serum CK test: Tests that measure an enzyme called creatine kinase (CK), or creatine phosphokinase, in the blood can be used to identify muscle defects. CK is an enzyme that helps carry out a chemical reaction on creatine, a substance used by muscle for energy. CK levels rise in the blood in patients with DMD when muscle cells deteriorate and CK leaks out. CK levels may also rise due to other factors, such as a heart attack or normal exercise. Therefore, the serum CK test may not be able to diagnose a patient specifically with DMD because other diseases that affect the muscles, as well as normal exercise, also result in increased levels of serum CK.
Biopsy: A doctor may surgically remove a small piece of muscle from patients in order to examine the muscle for signs of deterioration. A muscle biopsy may also be used to check for abnormal levels of the protein dystrophin. Patients with DMD are known to have reduced levels of this protein.
Genetic testing: Mutations in the dystrophin gene are known to cause DMD. Genetic tests can be used to check for these mutations and diagnose DMD. These tests may be used to confirm a diagnosis if there is a family history of DMD or if symptoms of DMD are present.
Gowers' sign: Some individuals with DMD may exhibit Gowers' sign, which may be useful in diagnosing the condition. Patients with Gowers' sign need to use their hands and arms to push themselves up when sitting (generally by moving the hands along the thighs). This is because patients with DMD may have difficulty standing due to weakness in leg muscles.
Infection: An infection of the lungs, especially pneumonia, is common in patients with DMD. This may be due to a weakness of respiratory muscles that reduces the ability of a patient to cough and leads to mucus buildup in the lungs.
Scoliosis: If the muscles of the back become weakened, they may become unable to hold the spine upright. This may lead to an abnormal curvature of the spine, called scoliosis. Individuals with scoliosis may have difficulty sitting in chairs and usually have back pain.
Respiratory muscles: In DMD, muscles in the lungs and diaphragm eventually deteriorate. This interferes with breathing, and difficulty breathing is the most common cause of death in patients with DMD. Most individuals with DMD do not survive past 30.
Cardiomyopathy: In some individuals with DMD, the muscles of the heart become enlarged and weakened. This may lead to an impaired ability to pump blood and may be life-threatening.
Currently, there is no known cure for DMD. Treatment generally focuses on managing the symptoms.
Assistive devices: Most patients with DMD lose the ability to walk. Leg braces or wheelchairs may be used to assist in moving.
Drugs: Experimental drugs are being tested in patients with DMD. These drugs may help treat the disease by allowing patients with DMD to make full-length dystrophin proteins. One drug that has been tested (called gentamicin) was found to be toxic to patients at high doses. Another similar drug currently being evaluated is PTC124, which may be less toxic and more effective at treating patients with DMD.
Physical therapy: Children with DMD may benefit from seeing a physical therapist. A physical therapist can help patients maintain muscle tone and keep muscles strong and flexible through performing different exercises.
Steroids: A steroid drug called prednisone, which can slow the rate of muscle deterioration, may be prescribed to patients with DMD. Prednisone has some side effects, including weight gain and loss of bone density.
Surgery: Some patients with DMD exhibit a deformity in the spine called scoliosis, in which the spine is abnormally curved. Surgery may be performed to partially correct this problem and reduce the extent of the abnormal curvature.
Transplantation: A heart transplant may be performed in some cases, if the deterioration of heart muscle is so severe that the heart is unable to pump enough blood.
Ventilator: Because many patients with DMD develop respiratory problems, a mechanical ventilator may be recommended by a doctor to assist with breathing. A mechanical ventilator is a machine that sends air into the lungs. Based on the severity of the respiratory problems, a ventilator may only be required during the night, or both during the day and at night.
Unclear or conflicting scientific evidence:
Coenzyme Q10: Coenzyme Q10 (CoQ10) is produced by the human body and is necessary for the basic functioning of cells. CoQ10 levels are reported to decrease with age and to be low in patients with some chronic diseases such as muscular dystrophies. Early studies in patients with muscular dystrophy taking CoQ10 supplements describe improvements in exercise capacity, heart function, and overall quality of life. Additional research is needed in this area.
Avoid in patients with allergy or hypersensitivity to CoQ10. Although few side effects are associated with CoQ10, there have been reports of nausea, stomach upset, or rash. Caution is advised in people who have bleeding disorders or who are taking drugs that increase the risk of bleeding. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Use cautiously in patients with liver disease as large doses of CoQ10 (greater than 300mg per day) may elevate aminotransferase levels. Use cautiously in patients with biliary obstruction or liver disease as these conditions may increase CoQ10 concentrations. CoQ10 may decrease blood pressure and caution is advised in patients with low blood pressure or in patients taking blood pressure medications. Elevations of liver enzymes have been reported rarely and caution is advised in people with liver disease or taking medications that may harm the liver. CoQ10 may lower blood levels of cholesterol or triglycerides. Thyroid hormone levels may be altered. There is not enough scientific evidence to support the safe use of CoQ10 during pregnancy or breastfeeding.
Creatine: Creatine is naturally synthesized in the human body from amino acids primarily in the kidney and liver and transported in the blood for use by muscles. Creatine loss is suspected to cause muscle weakness and breakdown in Duchenne muscular dystrophy. Further research of creatine supplementation for muscular dystrophy is needed before a recommendation can be made.
Avoid in patients with allergy or hypersensitivity to creatine. Use of creatine supplements has been associated with symptoms of asthma. There have been rare reports of loss of appetite, stomach upset, diarrhea, or nausea with creatine use. Avoid in patients with liver or kidney disease. Use caution with diabetes or low blood sugar. Creatine may cause muscle cramps or muscle breakdown, leading to muscle tears or discomfort. Weight gain and increased body mass may occur. Heat intolerance, fever, dehydration, reduced blood volume, or electrolyte imbalances (and resulting seizures) may occur. Chronic administration of a large quantity of creatine is reported to increase the production of formaldehyde, which may potentially cause serious unwanted side effects. Creatine may increase the risk of compartment syndrome of the lower leg, a condition characterized by pain in the lower leg associated with inflammation and ischemia (diminished blood flow), which is a potential surgical emergency. Creatine cannot be recommended during pregnancy or breastfeeding due to a lack of safety information.
Fair negative scientific evidence:
Selenium: Selenium is a mineral found in soil, water, and some foods. Selenium and vitamin supplementation has been studied in patients with Duchenne muscular dystrophy (DMD), myotonic dystrophy, and exercise-induced muscle injury. However, selenium does not appear to improve muscle strength or motor performance in patients with myotonic dystrophy. Despite promising early evidence, selenium supplementation does not appear to affect muscle strength or disease progression in muscular dystrophy.
Avoid if allergic or sensitive to products containing selenium. Avoid with a history of non-melanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
Traditional or theoretical uses lacking sufficient evidence:
Pantothenic acid: Pantothenic acid (vitamin B5) is found in many foods including meats, liver, kidney, fish/shellfish, chicken, vegetables, legumes, yeast, eggs, and milk. Although pantothenic acid has been suggested as a possible treatment for muscular dystrophy, research is currently lacking in this area.
Avoid if allergic to pantothenic acid or dexpanthenol. Avoid with gastrointestinal blockage. Pantothenic acid is generally considered safe in pregnant and breastfeeding women when taken at recommended doses.
Physical therapy: The goal of physical therapy is to improve mobility, restore function, reduce pain, and prevent further injury. A variety of techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used during physical therapy sessions. Physical therapy has been used to treat DMD, but research is limited in this area.
Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with their qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. However, physical therapy may aggravate some pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature, although causality is unclear. Erectile dysfunction has also been reported. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
Reishi mushroom: Reishi mushroom (Ganoderma lucidum), also known as ling zhi in China, grows on decaying logs and tree stumps. Reishi occurs in six different colors, but the red variety is most commonly used and commercially cultivated in East Asia and North America. Until human studies are performed, it remains unknown if reishi is beneficial for patients with muscular dystrophy.
Avoid if allergic or hypersensitive to any constituents of reishi mushroom or any member of its family. Use cautiously with diabetes, blood disorders (including hemophilia), low blood pressure, or ulcers. Avoid if pregnant or breastfeeding.
Vitamin E: Vitamin E exists in eight different forms ("isomers"): alpha, beta, gamma, and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Alpha-tocopherol is the most active form in humans. It is unclear if vitamin E is beneficial for patients with DMD. Human studies are currently lacking.
Avoid if allergic to vitamin E. For short periods of time, and in the recommended doses, vitamin E supplementation is generally considered safe. Avoid doses higher than 1,000 milligrams a day. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders.
There are currently no known ways to prevent DMD. However, genetic counseling for parents is available.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
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