Autosomal recessive genetic disease characterised by the accumulation of glycogen in cells throughout the body. There is an infantile-onset form, which manifests during the first year of life, and a late-onset form which appears 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 in the lysosomes. This accumulation impedes normal cellular functioning, leading to the death of the affected cells. The most affected tissues are muscle and neurons of the central nervous system.
Most cases present with muscle involvement of the shoulder girdle and pelvic girdle, with weakness in lifting the arms and in 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, the eyelids droop (ptosis), and there is difficulty in speaking and swallowing. When the digestive system is affected, they usually have weight loss without an apparent cause and gastrointestinal discomfort. They have faecal and urinary incontinence. When the musculoskeletal system is affected, they usually have scoliosis of the spine and vertebral fractures. They characteristically walk with a swaying of the hips known as "waddling gait". They suffer frequent falls and find it difficult to play sports. Finally, due to respiratory muscle involvement, they feel short of breath with minimal effort, hypoventilation during sleep with frequent apnoeas that cause daytime tiredness due to the lack of effective sleep during the night.
The diagnosis is suspected by detecting symptoms of weakness, usually in a regular check-up with the general practitioner. A blood test reveals the alteration of the enzyme acid alpha-glucosidase (GAA). It must then be confirmed with a genetic analysis that locates the mutation of the GAA gene; 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 develop symptoms in infancy, such as hypotonia, cardiac abnormalities, respiratory distress, feeding problems and growth retardation, usually do not live beyond 2 years of age without treatment.
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