Genetics

Pompe Disease

Pompe disease is caused by mutations in the GAA gene. Mutations in the GAA gene result in the deficiency of an enzyme, acid alpha-glucosidase, that is necessary for the breakdown of a particular fatty substance, glycogen. For patients with Pompe, glycogen cannot be broken down properly and becomes abnormally stored in a special area of the cell called the lysosome.

The continual accumulation of glycogen in lysosomes leads to progressive muscle weakness and damage. Pompe disease is classified based on the age at onset of symptoms and is either infantile or late-onset. In infantile Pompe disease, symptoms appear shortly after birth with significant muscle weakness including the muscles of the heart (cardiomyopathy) and the respiratory muscles. Late-onset Pompe disease may present in childhood or later in life and is slowly progressive with the primary muscles affected in the trunk, girdle muscles (shoulders and ships), and diaphragm. Everyone has two copies of the GAA gene, and to have Pompe disease both copies of the gene must have mutations. This is called autosomal recessive inheritance.

When Pompe disease is suspected either on the basis of clinical signs and symptoms or by the discovery of a relative with Pompe disease, the diagnosis can be confirmed by a simple blood test that measures the activity of the enzyme acid alpha-glucosidase. In addition, genetic testing can be done to analyze the GAA gene, to see if there are any errors in the gene that could explain why the enzyme is not working properly. This is called mutation analysis. The use of molecular genetic analysis in patients to identify the exact error in the acid alpha-glucosidase gene (the patient's "genotype") can sometimes be used as an aid in attempting to predict the severity of disease (the patient's "phenotype").

Pompe Disease Treatment

While there is no cure for Pompe disease, treatment options are available. Enzyme Replacement Therapy (ERT) is used to replace the enzyme acid alpha-glucosidase that is missing or not working properly in people with Pompe disease. Lumizyme is the only FDA-approved treatment in the U.S. for the treatment of Pompe disease. It is given via intravenous (IV) infusion every 2 weeks and life-long treatment is recommended. For infantile-onset Pompe disease, ERT is best started before severe symptoms occur especially involving the heart.