Pompe Disease

Pompe disease, glycogen storage disease type II, is a rare inherited disorder caused by the buildup of glycogen (a complex form of sugar stored for energy) in the body’s cells. It is estimated that Pompe disease occurs in about 1 in every 40,000 births. Pompe disease is caused by mutations in the gene that make the enzyme alpha-glucosidase (GAA) which is located in lysosomes. Lysosomes ingest glycogen which is then converted by the GAA into glucose which fuels the muscle. In Pompe disease, there is a deficient amount of GAA which causes an accumulation of glycogen in certain organs, tissues, and muscles which impairs normal function. There are up to 300 different mutations in the GAA that cause symptoms of Pompe disease that vary in severity. The severity and the age of onset correspond to the degree of enzyme deficiency.
Early onset symptoms are the result of complete/near complete deficiency of the enzyme. This is found in infants with symptoms beginning in the first few months of life. Symptoms may include feeding problems, poor weight gain, enlarged tongues, muscle weakness, flaccidity of the muscles and more. Respiratory difficulties may result from lung infections. The heart is also enlarged greatly, almost resembling a heart with HCM. Late onset, occurring in juveniles and adults, is caused by a partial deficiency of GAA. Symptoms may occur as early as 10 years old or as late as 60 years old. Symptoms include muscle weakness which progresses to respiratory weakness and possibly death. The heart is usually not involved in the late onset.
A diagnosis can be confirmed by screening for the common genetic mutations or testing the level of the GAA enzyme. Once one member has been diagnosed, testing of other family members and consultation with a geneticist is recommended. Carriers can be identified through the genetic mutation analysis. Treatment includes enzyme replacement therapy which has proven to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation in infants. Alglucosidase alfa (Myozyme©) has received FDA approval for the treatment of infants and children with Pompe disease. Another drug, Lumizyme © , has been approved for late onset Pompe disease. Consultation from a doctor is recommended before beginning any new treatment.
Figure 1: Development of facial muscle weakness in patient 1 (a, b) and patient 2 (c, d) with infantile-onset Pompe disease. Facial muscle weakness, present in patient 1 in both stages, is absent in patient 2 for both stages.