|
 What is Limb-Girdle Muscular Dystrophy?
 |
| LGMD primarily affects the muscles around the hips and shoulders. |
Limb-girdle muscular dystrophy (LGMD) isn’t really one disease. It’s a group of disorders affecting voluntary muscles, mainly those around the hips and shoulders — the pelvic and shoulder girdles, also known as the limb girdles.
You also may hear the term proximal used to describe the muscles that are most affected in LGMD. The proximal muscles are those closest to the center of the body; distal muscles are farther away from the center (for example, in the hands and feet). The distal muscles are affected late in LGMD, if at all.
Over time (usually many years), the person with LGMD loses muscle bulk and strength. Eventually, he may need a power wheelchair or scooter, especially for long distances.
LGMD can begin in childhood, adolescence, young adulthood or even later. Both genders are affected equally. When limb-girdle muscular dystrophy begins in childhood, some physicians say, the progression is usually faster and the disease more disabling. When the disorder begins in adolescence or adulthood, they say, it’s generally not as severe and progresses more slowly.
What are the forms of limb-girdle muscular dystrophy?
There are at least 19 forms of LGMD, and they’re classified by the genetic flaws that appear to cause them (see “Known Forms of Limb-Girdle Muscular Dystrophy"). As of 2007, 15 specific genes that lead to production of muscle proteins have been implicated as definite causes of LGMD when they’re flawed. MDA research was behind much of the work that identified these LGMD genes.
Genes, located on chromosomes in each cell in the body, are the codes, or recipes, for production of the body’s various proteins. The genes associated with LGMD normally make proteins necessary for muscle function.
When protein problems arise because one of these genes is faulty, fibers in the muscles don’t work properly. Gradually, the muscles become weak enough that people experience the symptoms of limb-girdle muscular dystrophy. Because LGMD is progressive, the muscles continue to get weaker throughout the person’s lifetime.
Six of the genes that, when flawed, cause LGMD lead to production of proteins that are normally located in the muscle cell membrane. (The membrane is a thin sheath that surrounds each muscle cell, helping to protect it from injury during muscle contraction.) If any of these proteins is missing because the gene for it is flawed, the membrane probably loses some of its “shock absorber” qualities and has a harder time protecting the muscle cell from injury during normal contraction and relaxation cycles.
 |
| Eventual loss of walking ability is common in LGMD, but some people walk longer than others. |
In LGMD, the muscle membrane also may be “leaky,” letting substances in or out that are supposed to stay on one side of the membrane or the other. Membrane proteins, when they’re made correctly and are in their normal positions, may also perform other essential functions in the cell; these functions may be defective when one or more of the proteins are absent.
Not all of the muscle proteins associated with LGMD are in the membrane, however. For instance, calpain-3 is probably located in the main part of the muscle cell, and myotilin and telethonin are located in the part of the muscle cell that allows it to contract and relax.
The types of LGMD are generally classified by letters and numbers that indicate which gene is known or suspected to be involved and whether the disorder is inherited as a dominant or recessive condition, meaning whether one or two flawed genes are needed to cause it. (See “Does It Run in the Family?”) Some physicians classify LGMD according to which protein is missing or deficient, if this is known. For example, one form may be called alpha-sarcoglycan deficiency, and another is known as beta-sarcoglycan deficiency. In the future, the term limb-girdle muscular dystrophy may become obsolete and be replaced by more specific terms.
SINGLE MUSCLE CELL |
|
The muscles most affected in limb-girdle muscular dystrophy (LGMD) are those surrounding the shoulders and hips, with nearby muscles in the upper legs and arms sometimes also weakening with time. These muscles are shown in red.
Inside each muscle cell, many proteins, some of which are shown here in blue and yellow-orange, help the cell contract and protect it from the stress of contractions.
When any of the proteins shown here in yellow-orange are missing or nonfunctional, LGMD is the result. At least six of these proteins are normally found in the muscle cell membrane, a sheath surrounding each cell. They form part of the structure of the membrane. Determining which proteins are missing in LGMD and what their normal functions are in the muscle cell are crucial steps in developing treatments. |
How fast does LGMD progress?
It’s not yet possible to predict the course of LGMD in an individual.
Some forms of the disorder progress to loss of walking ability within a few years and cause serious disability, while others progress very slowly over many years and cause minimal disability. At this time, progression in each type of LGMD can’t be predicted with certainty, although knowing the genetic mutation underlying your disease can be helpful.
What happens along the way?
 |
| A wheelchair or scooter, such as the one this physician with LGMD uses, becomes convenient when weakness in the pelvic girdle and upper legs causes frequent falls. |
Often, people with LGMD first notice a problem when they begin to walk with a “waddling” gait because of weakness of the hip and leg muscles. They may have trouble getting out of chairs, rising from a toilet seat or climbing stairs.
Weakness in the shoulder area may make reaching over the head, holding the arms outstretched or carrying heavy objects difficult. It may become increasingly hard to keep the arms above the head for such activities as combing your hair or arranging things on a high shelf. Some people find it harder to type on a computer or other keyboard and may even have trouble feeding themselves.
Assistive devices, such as a cane or a long-handled reacher, can make things easier as weakness progresses.
A power wheelchair or scooter becomes convenient when weakness in the pelvic girdle and upper legs causes frequent falls. People whose LGMD has reached this stage often find that a great deal of their independence returns, and they’re much less fatigued, when they begin using this type of vehicle.
The heart can be affected in LGMD, but this doesn’t occur as often as it does in some other forms of muscular dystrophy. Heart problems can take two forms — weakness of the heart muscle (cardiomyopathy) and abnormal transmission of signals that regulate the heartbeat (conduction abnormalities or arrhythmias). The heart should be monitored for these complications. When necessary, medications or devices (such as pacemakers) can be used to treat them.
Respiratory (breathing) function can decline over time, and this, too, should be monitored regularly. There are devices that can help sustain respiratory function.
What's not affected in LGMD?
LGMD, like other muscular dystrophies, is primarily a disorder of voluntary muscles. These are the muscles you use to move the limbs, neck, trunk and other parts of the body that are under voluntary control.
 |
| LGMD doesn’t impair the intellect, the senses or the desire for a challenge. |
The involuntary muscles, except for the heart (which is a special type of involuntary muscle), aren’t affected in LGMD.
Digestion, bowel and bladder functions and sexual function, which are carried out by involuntary muscles, remain normal.
Severe pain isn’t a major part of LGMD, although limited mobility sometimes leads to muscle soreness and aching joints. Exercises to keep joints limber, moving around as much as possible, warm baths and, if needed, medication can keep this kind of discomfort to a minimum.
The brain, the intellect and the senses are unaffected in LGMD. People with LGMD can think, see, hear and feel sensations as well as those without muscular dystrophy.
What tests are used to diagnose LGMD?
In diagnosing any form of muscular dystrophy, a doctor usually begins by taking a patient and family history and performing a physical examination. Much can be learned from these, including the pattern of weakness. The history and physical go a long way toward making the diagnosis, even before any laboratory tests are done.
 |
| The diagnostic process usually begins with a history and physical examination. |
The doctor also wants to determine whether the patient’s weakness results from a problem in the muscles themselves or in the nerves that control them. Problems with muscle-controlling nerves, or motor nerves, originating in the spinal cord and reaching out to all the muscles, can cause weakness that looks like a muscle problem but really isn’t.
Usually, the origin of the weakness can be pinpointed by a physical exam. Occasionally, special testing called electromyography is done. In this kind of test, the electrical activity of the muscles is measured and nerves stimulated to see where the problem lies. Electromyography is uncomfortable but not usually very painful.
A nerve conduction study also may be done. This too is uncomfortable, but not seriously painful.
Early in the diagnostic process, doctors often order a special blood test called a CK level. CK stands for creatine kinase, an enzyme that leaks out of damaged muscle. When elevated CK levels are found in a blood sample, it usually means muscle is being destroyed by some abnormal process, such as a muscular dystrophy or inflammation. Therefore, a high CK level suggests that the muscles themselves are the likely cause of the weakness, but it doesn’t tell exactly what the muscle disorder might be.
 |
| An echocardiogram (ultrasound imaging of the heart) can be used to monitor heart function in LGMD. |
Today, DNA testing to look for genetic flaws that are known to cause LGMD is available for several forms of the disease and is rapidly expanding. If a particular type of LGMD is suspected, DNA testing, using a blood sample, may be undertaken relatively early in the diagnostic process, often before the doctor considers a more invasive procedure.
In some cases it is necessary for a doctor to order a muscle biopsy, the surgical removal of a small sample of muscle from the patient. By examining this sample, doctors can tell a great deal about what’s actually happening inside the muscles. Using a variety of techniques, muscular dystrophies can be distinguished from inflammatory and other disorders. Specific testing of the biopsy also may distinguish among different forms of muscular dystrophy.
Tests on the biopsy sample also can provide information about which muscle proteins are present in the muscle cells, and whether they’re present in the normal amounts and in the right locations. This can tell the doctor and patient what’s wrong with the cells’ proteins and provide likely candidates as to which genes are responsible for the problem. The correlation between missing proteins on the muscle biopsy and genetic flaws isn’t perfect, however.
Is it important to find out what genetic type of LGMD a person has?
At this time, genetic testing to determine an individual’s exact type of LGMD is commercially available for only some LGMD forms. If there are clues as to what gene is involved (from previously tested family members, biopsy findings or symptoms clearly associated with one or two types of LGMD), it may be practical to do DNA testing to pinpoint the gene defect. However, if there are no such clues, testing for more than a dozen genetic defects is available but extremely expensive.
Understanding your inheritance pattern may, however, be important for family planning. Your family history can help determine the inheritance pattern of your disorder.
Treatment for LGMD, mainly involving physical and occupational therapy, assistive devices, and monitoring for heart and breathing complications, is essentially the same in all forms of the disease. An individual’s precise genetic defect makes little difference in these interventions.
Can special diets help in LGMD?
At this time, no special dietary restrictions or additions are known to help in LGMD.
Many people, when they hear the words “lack of a protein,” logically ask, “Should I eat more protein?” Unfortunately, eating more protein than your normal requirement has no effect on any of the proteins missing in LGMD. It’s true that when you eat a steak, you’re ingesting many muscle proteins (from the cow). Your body then breaks down these proteins into their component parts and uses them to build its own proteins. But a person who lacks the genetic instructions to make these new proteins won’t be able to make them no matter how much protein he eats.
A doctor may advise a weight reduction or weight stabilization diet for some people with LGMD. Being markedly overweight puts greater stress on already weakened muscles.
Does it Run in the Family?
On being told they have a genetic disorder such as LGMD, bewildered patients often ask, “But it doesn’t run in the family, so how could it be genetic?”
LGMD can run in a family, even if only one person in the biological family has it. This is because of the ways in which genetic diseases are inherited.
LGMD can be inherited in one of two basic ways, known as the autosomal dominant pattern and the autosomal recessive pattern. “Known Forms of LGMD” shows which types follow each pattern.
The word autosomal means that the genes involved aren’t on the X or Y chromosome and, therefore, don’t have a preference for either men or women.
In diseases with dominant inheritance patterns, a person who inherits a flawed gene from one parent will have disease symptoms. That parent would also have the disease.
In diseases with recessive inheritance, a person must inherit two flawed genes — one from each parent — to have disease symptoms. The parents don’t have symptoms.
A recessive form of LGMD can show up in one person when there’s no family history. Other family members may have been carriers, having no disease symptoms. Carriers have the genetic flaw (mutation) on a chromosome and can have a child with the disease, but only if the child’s other parent is also a carrier. So it isn’t unusual for carriers of a rare recessive disease not to know they’re carriers until someone in the family develops the disease.
Just to make things a little more complicated, a person with LGMD may have a brand new genetic mutation (after all, they have to start somewhere), so there may really be no family history or even carriers of the disorder in the family. However, once someone develops a genetic disease, even if the mutation is spontaneous (new) with that person, he or she can then pass on the mutation to any offspring, thereby introducing the gene for the disease into the family.
The details of inheritance risks for any particular form of LGMD depend on many circumstances, including exactly which type of LGMD has been diagnosed. A good way to find out more is to talk to your MDA clinic physician or ask to see the genetic counselor at the MDA clinic. You also can read MDA’s booklet “Facts About Genetics and Neuromuscular Diseases.”
|
Are there any special exercises that can help?
 |
| Some experts recommend swimming and water exercises to keep muscles toned. |
A physical therapy program is usually part of the treatment for LGMD. Your MDA clinic physician may refer you to the physical therapy department at your medical center for a thorough evaluation and an individualized exercise program.
The primary goals of physical therapy are to allow greater motion in the joints and to prevent contractures (freezing of the joints). These problems can arise when movement is limited, and it’s important for the patient’s comfort and function to avoid them.
Doctors and therapists have somewhat different opinions on the relative value or danger of various exercise regimens in people with muscular dystrophy. In LGMD, certain kinds of stress-causing exercises may actually hasten muscle damage.
 |
| An important goal of physical therapy is to allow greater motion in the joints. |
Some experts recommend swimming and water exercises as a good way to keep muscles as toned as possible without causing undue stress on them. The buoyancy of the water helps protect against certain kinds of muscle strain and injury. Before undertaking an exercise program, make sure you’ve had a cardiac evaluation. And don’t swim alone.
Occupational therapy focuses more on specific activities and functions, particularly use of the hands, while physical therapy emphasizes mobility and (where possible) strengthening of large muscle groups. Your MDA clinic also can refer you to the occupational therapy department, where you can receive help with tasks related to your job, recreation or daily living. For example, arm supports can make tasks such as using a computer or fixing your hair less tiring.
|
