Limb-Girdle Muscular Dystrophy (LGMD)

Diagnosis

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 doctor also will want to determine whether a patient's weakness results from a problem in the muscles themselves (as is the case in muscular dystrophy), or in the muscle-controlling nerves, called motor neurons, that control them.

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 does not tell exactly what the muscle disorder might be.

Sometimes, 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.

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. Prior to muscle biopsy, less-invasive genetic testing is typically recommended. A muscle biopsy is appropriate if genetic and protein testing for LGMD are uninformative or unavailable. By examining a muscle sample, doctors can tell a great deal about a potential diagnosis. 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 are present in the normal amounts and in the right locations. The correlation between missing proteins in the muscle biopsy and genetic flaws is not perfect.

DNA testing is available for several forms of LGMD and is rapidly expanding. If a particular type of LGMD is suspected, DNA testing (from a blood sample) may be undertaken relatively early in the diagnostic process, often before the doctor considers more invasive procedures.

Commercially available genetic testing can determine an exact type of LGMD. 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 can get very expensive. Next-generation sequencing is an option if targeted genetic testing and muscle biopsy do not support a clear diagnosis.

Understanding your inheritance pattern may be important for family planning. Your family history can help determine the inheritance pattern of your disorder.

Sanofi Genzyme is collaborating with Revvity Omics to offer a complimentary genetic testing program called The Lantern Project that offers diagnostic testing for several disorders, such as Pompe disease, LGMD, Gaucher, and others.

The Lantern project helps patients to get a better and more precise genetic diagnosis. Patients with clinical symptoms suggesting LGMD or those who has unspecified LGMD genetic diagnosis, are eligible to apply. Additionally, patients with the physical manifestation of Pompe disease, or those who screened positive for Pompe are welcome to participate as well. For more details about the program please visit The Lantern Project website.

Participants will be tested against 98 different genes that are known to cause LGMD, Pompe (GAA genetic variants), other myopathies, and myasthenic syndrome in order to provide them with better diagnosis.

For more information about a genetic testing program at no cost to families, visit the Lantern Project.

No matter the exact genetic cause, treatment is essentially the same for all forms of LGMD — physical and occupational therapy, assistive devices, and monitoring for heart and breathing complications.