There are more than 30 different types of LGMD, and each type is caused by a specific genetic mutation. LGMD is a rare condition, affecting about 1 in 14,500 people. It can affect people of any age, but it most commonly appears in adolescence or early adulthood.
Clinical Presentation
The clinical presentation of LGMD can vary depending on the subtype, but some common symptoms include:
- Progressive weakness in the hip and shoulder muscles
- Difficulty with running, jumping, and climbing stairs
- Proximal muscle weakness (muscles closer to the center of the body)
- Muscle wasting
- Muscle pain and cramps
- Respiratory and cardiac involvement in some subtypes
Family History
Physical Examination
A thorough physical examination is essential in the diagnosis of LGMD. The exam may reveal:
- Weakness in the proximal muscles
- Gait abnormalities
- Muscle wasting
- Tendon reflexes may be reduced or absent
- Hypertrophy of the calves (enlarged calf muscles) in some subtypes
Electromyography (EMG) and Nerve Conduction Studies (NCS)
EMG and NCS are tests that measure the electrical activity of muscles and nerves. These tests may be useful in diagnosing LGMD by showing evidence of muscle damage or abnormal muscle activity.
Symptoms of LGMD
The symptoms of LGMD vary depending on the type of the disease. However, most people with LGMD experience muscle weakness and wasting in the muscles around the shoulder and hip girdles, which makes it difficult to lift the arms or walk. Other common symptoms include:
- Difficulty standing up from a seated position
- Difficulty climbing stairs or walking long distances
- Toe-walking or waddling gait
- Muscle cramps and stiffness
- Back pain
- Fatigue
As the disease progresses, people with LGMD may also experience respiratory problems, heart problems, and difficulty swallowing.
Diagnosis of LGMD
The diagnosis of LGMD starts with a careful evaluation of the patient’s medical history and a physical examination. The physician will look for signs of muscle weakness and wasting, which are the hallmark symptoms of LGMD. They will also assess the patient’s gait, posture, and range of motion. The physician may order blood tests to measure the levels of creatine kinase (CK), an enzyme that is released into the blood when muscles are damaged. Elevated levels of CK are a common finding in LGMD, but they are not specific to the disease.
To confirm the diagnosis of LGMD, genetic testing is required. LGMD is caused by mutations in at least 35 genes, and the specific gene involved varies depending on the subtype of LGMD. Genetic testing can be done using a variety of techniques, including sequencing, deletion/duplication analysis, and targeted mutation analysis.
Next-generation sequencing (NGS) has revolutionized the field of genetic testing by allowing for the simultaneous analysis of multiple genes at a reduced cost and turnaround time. NGS can identify the causative mutation in up to 70% of LGMD cases.
It is important to note that the diagnosis of LGMD can be challenging due to the overlap of symptoms with other neuromuscular disorders.
The doctor may also order a variety of tests, including:
- Blood tests to look for genetic mutations or signs of muscle damage
- Electromyography (EMG) to measure electrical activity in the muscles
- Nerve conduction studies to measure how well the nerves that control the muscles are working
- Muscle biopsy to examine a sample of muscle tissue under a microscope
Israeli researchers have discovered a new drug that reverses this deadly disease.
The drug was administered to a patient who was near death, completely immobile, and fully dependent on artificial ventilation, for over a year.
Not only did she stop deteriorating, she has improved dramatically: she can breathe without support for hours at a time, move her arms and legs extensively, and even feed her grandchild.
This was the first time a human had been treated with the drug. Until this point, the research team had been testing the novel medication’s safety in mice.
They were given a compassionate use permit to use it, which allows terminally ill patients who meet certain medical criteria access to drugs still undergoing clinical trials.
Other patients, some of whom are already in late stages of limb girdle muscular disease (LGMD), are awaiting treatment.
LGMD develops around the age of 40 years, progressing to complete immobility of the limbs and chest muscles by the early 50s, necessitating full-time ventilation and eventually culminating in death.
The disease is caused by a mutation in the gene encoding an enzyme, which prevents it from creating cholesterol and other medical products like it is supposed to.
The novel drug, which was developed by researchers from the Ben Gurion University of the Negev and the Soroka Medical Center, contains a synthesized product that this enzyme normally creates (methylmevalonolactone) which patients with LGMD lack.
The researchers estimate that there are dozens to hundreds of people affected by this hereditary disease that could benefit from this effective, life-saving treatment.
They also believe that the drug could treat muscle symptoms that some users of statins, the most commonly used medication in lowering blood cholesterol, experience months after they stop taking the treatment.
In mouse models mimicking humans who experience these symptoms, the medication was shown to be very effective.
The study, published recently in the Proceedings of the National Academy of Sciences (PNAS), was supported by the Israel Science Foundation.
