What Is Know About The Genetics Of Pompe Disease And How Do These Genetics Affect Pompe Disease Symptoms?
Pompe disease is attributable to mutations in a gene that is designated GAA, which encodes the protein alpha-glucosidase. The normal function of alpha-glucosidase is to break down the complex sugar glycogen into glucose, which is the main energy source of cells. Mutations in the GAA gene affect the ability of alpha-glucosidase to break down glycogen, and therefore glycogen builds up to abnormally high levels in individuals who are mutant in the GAA gene. Unfortunately, this abnormal build up of glycogen causes damage to the various organs and tissues, and particularly the muscles, of the body.
To date, more than 70 mutations in the GAA have been identified, and it is known that the severity of symptoms that Pompe disease suffer from is dependent of which particular mutation or mutations they inherit. Some mutations drastically, if not completely, limit the function of alpha-glucosidase, typically either by reducing or preventing its synthesis in cells. Since Pompe disease is an autosomal recessive disorder, people who have two copies of the GAA gene which have mutations of this severe kind usually experience early onset Pompe disease. This form of Pompe disease strikes at an early age, and typically within the first few months of life. Infants having the early onset form of Pompe disease generally do not grow as quickly as do normal infants, exhibit feeding problems, have poor muscle function, are prone to respiratory problems and lung infections, and have enlarged tongues and hearts. Sadly, most infants who have early onset Pompe disease die within the first 12 months of life if these symptoms are not properly treated.
Other GAA mutations are not as severe. These mutations somewhat diminish, but do not nearly completely inhibit, the normal function of alpha-glucosidase. People who have who have two copies of the GAA gene which have mutations of this variety generally do not experience Pompe disease symptoms in infancy, but instead first experience these symptoms anywhere from later childhood to about age 50 or so (therefore, this is referred to as the late onset form of Pompe disease). Once Pompe disease first arises in these individuals, muscle weakness, respiratory failure, and death then follow within a few years or so thereafter if the disease is left untreated.