An autosomal recessive genetic disease characterized by the accumulation of glycogen in the cells of the entire organism. There is an infantile-onset form that manifests during the first year of life and a late-onset form that manifests either in childhood or at any time during adulthood.
It is caused by a deficiency of the enzyme acid alpha-glucosidase, which is necessary for the breakdown of glycogen within the lysosomes. This accumulation interferes with normal cellular function and leads to the death of the affected cells. The most affected tissues are muscle and central nervous system neurons.
Most cases present with muscular involvement of the shoulder girdle and pelvic girdle, with weakness when lifting arms and climbing stairs or getting up from a chair. More than half of the patients have respiratory insufficiency with exercise intolerance.
When the facial muscles are affected, there is drooping of the eyelids (ptosis), and difficulty speaking and swallowing. When the digestive system is affected, they usually have weight loss without apparent cause and gastrointestinal discomfort. They also have fecal and urinary incontinence. If the musculoskeletal system is affected, they usually have scoliosis of the spine and vertebral fractures. Characteristically, they walk with a swaying of the hips, known as a "waddling gait". They are prone to falls and have difficulty playing sports. Finally, due to the involvement of the respiratory musculature, they experience shortness of breath with minimal exertion, hypoventilation during sleep with frequent apneas, which causes daytime fatigue due to lack of effective sleep during the night.
Diagnosis is suspected when symptoms of weakness are observed, usually during a visit to the family doctor. The diagnosis is made with a blood sample that shows the alteration of the enzyme acid alpha-glucosidase (GAA). It must then be confirmed by genetic analysis to locate the GAA gene mutation; to date, more than 300 mutations are known.
Treatment is based on the administration of the enzyme alglucosidase alfa (Myozyme®).
It is very important to diagnose the disease as early as possible in order to delay the progression of symptoms and prevent early death. Patients who present in infancy with symptoms such as hypotonia, cardiac changes, respiratory distress, feeding problems and growth retardation usually do not survive beyond 2 years without treatment.
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